VCV000039020.28 - ClinVar

NM_024312.5(GNPTAB):c.1042A>C (p.Ile348Leu)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(14)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Benign/Likely benign

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_024312.5(GNPTAB):c.1042A>C (p.Ile348Leu)

Variation ID: 39020 Accession: VCV000039020.28

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 12q23.2 12: 101770477 (GRCh38) [ NCBI UCSC ] 12: 102164255 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Apr 4, 2013	Sep 29, 2024	Feb 1, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_024312.5:c.1042A>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_077288.2:p.Ile348Leu	missense
NC_000012.12:g.101770477T>G
NC_000012.11:g.102164255T>G
NG_021243.1:g.65391A>C
	Q3T906:p.Ile348Leu

... more HGVS ... less HGVS

Protein change

I348L

Other names

Canonical SPDI

NC_000012.12:101770476:T:G

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

0.01198 (G)

Allele frequency Help The frequency of the allele represented by this VCV record.

Exome Aggregation Consortium (ExAC) 0.00375

1000 Genomes Project 0.01198

The Genome Aggregation Database (gnomAD) 0.01289

Trans-Omics for Precision Medicine (TOPMed) 0.01292

1000 Genomes Project 30x 0.01312

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.01346

Links

ClinGen: CA343333 UniProtKB: Q3T906#VAR_027510 dbSNP: rs7958709 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
GNPTAB		-	-	GRCh38 GRCh37	1561	1582

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Mucolipidosis type II	Likely benign (4)	criteria provided, multiple submitters, no conflicts	May 28, 2019	RCV000032285.10
not specified	Benign/Likely benign (3)	criteria provided, multiple submitters, no conflicts	Dec 10, 2021	RCV000250304.9
not provided	Likely benign (4)	criteria provided, multiple submitters, no conflicts	Mar 24, 2019	RCV000437039.11
Pseudo-Hurler polydystrophy	Likely benign (1)	criteria provided, single submitter	Apr 28, 2017	RCV000344025.5
Mucolipidosis type II Pseudo-Hurler polydystrophy	Benign/Likely benign (2)	criteria provided, multiple submitters, no conflicts	Feb 1, 2024	RCV001079378.9

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	NOT SPECIFIED Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV000314274.1 First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016
Likely benign (Apr 28, 2017)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Mucolipidosis type II Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000375436.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Publications: PubMed (2) PubMed: 25505245‚ 19617216 Comment: This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more) This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
Likely benign (Apr 28, 2017)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Pseudo-Hurler polydystrophy Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000375435.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Publications: PubMed (2) PubMed: 25505245‚ 19617216 Comment: This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more) This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
Likely benign (Mar 24, 2019)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV001816620.1 First in ClinVar: Sep 08, 2021 Last updated: Sep 08, 2021	Comment: This variant is associated with the following publications: (PMID: 27884173, 19617216, 25505245, 22995991)
Benign (Feb 01, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Pseudo-Hurler polydystrophy Mucolipidosis type II Explanation for multiple conditions: Uncertain. The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases. Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001122615.6 First in ClinVar: Dec 17, 2019 Last updated: Feb 28, 2024
Likely Benign (Jan 24, 2017)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not provided Affected status: not provided Allele origin: germline	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics Accession: SCV000511822.1 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017	Comment: Converted during submission to Likely benign.
Likely benign (May 28, 2019)	criteria provided, single submitter (Mendelics Assertion Criteria 2017) Method: clinical testing	Mucolipidosis type II Affected status: unknown Allele origin: unknown	Mendelics Accession: SCV001138795.1 First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020
Benign (Mar 25, 2020)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not specified Affected status: yes Allele origin: germline	Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital Accession: SCV001984551.1 First in ClinVar: Oct 30, 2021 Last updated: Oct 30, 2021
Likely benign (Dec 10, 2021)	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV002051009.1 First in ClinVar: Jan 08, 2022 Last updated: Jan 08, 2022
Likely benign (Sep 09, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Mucolipidosis type II Pseudo-Hurler polydystrophy Affected status: unknown Allele origin: unknown	Fulgent Genetics, Fulgent Genetics Accession: SCV002795038.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022
Likely benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: not provided	not provided (Autosomal recessive inheritance) Affected status: yes Allele origin: germline	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005216773.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024
Benign (Sep 27, 2017)	no assertion criteria provided Method: clinical testing	not provided Affected status: unknown Allele origin: unknown	Mayo Clinic Laboratories, Mayo Clinic Accession: SCV000800956.1 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017
Benign (Jan 09, 2020)	no assertion criteria provided Method: clinical testing	Mucolipidosis type II Affected status: unknown Allele origin: germline	Natera, Inc. Accession: SCV001463446.1 First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021
not provided (-)	no classification provided Method: literature only	Mucolipidosis type II Affected status: not provided Allele origin: unknown	GeneReviews Accession: SCV000055928.2 First in ClinVar: Apr 04, 2013 Last updated: Oct 01, 2022	Publications: PubMed (2) PubMed: 19617216‚ 20301728 BookShelf: NBK1828 BookShelf: NBK1828
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Comment:

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.

Comment:

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
GNPTAB-Related Disorders.	Adam MP	-	2019	PMID: 20301728
Analysis of mucolipidosis II/III GNPTAB missense mutations identifies domains of UDP-GlcNAc:lysosomal enzyme GlcNAc-1-phosphotransferase involved in catalytic function and lysosomal enzyme recognition.	Qian Y	The Journal of biological chemistry	2015	PMID: 25505245
Phenotype and genotype in mucolipidoses II and III alpha/beta: a study of 61 probands.	Cathey SS	Journal of medical genetics	2010	PMID: 19617216

Text-mined citations for rs7958709 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Sep 29, 2024

ClinVar Genomic variation as it relates to human health

NM_024312.5(GNPTAB):c.1042A>C (p.Ile348Leu)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs7958709 ...