VCV000038482.19 - ClinVar

NM_001370658.1(BTD):c.152T>C (p.Leu51Pro)

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.

(6)

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.

Conflicting classifications of pathogenicity
Uncertain significance(1); Benign(2); Likely benign(2)

criteria provided, conflicting classifications

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001370658.1(BTD):c.152T>C (p.Leu51Pro)

Variation ID: 38482 Accession: VCV000038482.19

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 3p25.1 3: 15635591 (GRCh38) [ NCBI UCSC ] 3: 15677098 (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	Feb 20, 2024	Jan 11, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_001370658.1:c.152T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001357587.1:p.Leu51Pro	missense
NM_000060.4:c.212T>C	NP_000051.1:p.Leu71Pro	missense
NM_001281723.4:c.152T>C	NP_001268652.2:p.Leu51Pro	missense
NM_001281724.3:c.152T>C	NP_001268653.2:p.Leu51Pro	missense
NM_001281725.3:c.152T>C	NP_001268654.1:p.Leu51Pro	missense
NM_001281726.3:c.152T>C	NP_001268655.2:p.Leu51Pro	missense
NM_001323582.2:c.152T>C	NP_001310511.1:p.Leu51Pro	missense
NM_001370752.1:c.152T>C	NP_001357681.1:p.Leu51Pro	missense
NM_001370753.1:c.152T>C	NP_001357682.1:p.Leu51Pro	missense
NM_001407364.1:c.152T>C	NP_001394293.1:p.Leu51Pro	missense
NM_001407365.1:c.152T>C	NP_001394294.1:p.Leu51Pro	missense
NM_001407366.1:c.152T>C	NP_001394295.1:p.Leu51Pro	missense
NM_001407367.1:c.152T>C	NP_001394296.1:p.Leu51Pro	missense
NM_001407368.1:c.152T>C	NP_001394297.1:p.Leu51Pro	missense
NM_001407369.1:c.152T>C	NP_001394298.1:p.Leu51Pro	missense
NM_001407370.1:c.152T>C	NP_001394299.1:p.Leu51Pro	missense
NM_001407371.1:c.152T>C	NP_001394300.1:p.Leu51Pro	missense
NM_001407372.1:c.152T>C	NP_001394301.1:p.Leu51Pro	missense
NM_001407373.1:c.152T>C	NP_001394302.1:p.Leu51Pro	missense
NM_001407374.1:c.152T>C	NP_001394303.1:p.Leu51Pro	missense
NM_001407375.1:c.152T>C	NP_001394304.1:p.Leu51Pro	missense
NM_001407376.1:c.152T>C	NP_001394305.1:p.Leu51Pro	missense
NM_001407377.1:c.152T>C	NP_001394306.1:p.Leu51Pro	missense
NM_001407378.1:c.152T>C	NP_001394307.1:p.Leu51Pro	missense
NM_001407379.1:c.152T>C	NP_001394308.1:p.Leu51Pro	missense
NM_001407380.1:c.152T>C	NP_001394309.1:p.Leu51Pro	missense
NM_001407381.1:c.152T>C	NP_001394310.1:p.Leu51Pro	missense
NM_001407382.1:c.152T>C	NP_001394311.1:p.Leu51Pro	missense
NM_001407383.1:c.152T>C	NP_001394312.1:p.Leu51Pro	missense
NM_001407384.1:c.152T>C	NP_001394313.1:p.Leu51Pro	missense
NM_001407386.1:c.152T>C	NP_001394315.1:p.Leu51Pro	missense
NM_001407388.1:c.152T>C	NP_001394317.1:p.Leu51Pro	missense
NM_001407390.1:c.152T>C	NP_001394319.1:p.Leu51Pro	missense
NM_001407392.1:c.152T>C	NP_001394321.1:p.Leu51Pro	missense
NM_001407394.1:c.152T>C	NP_001394323.1:p.Leu51Pro	missense
NM_001407395.1:c.152T>C	NP_001394324.1:p.Leu51Pro	missense
NM_001407396.1:c.152T>C	NP_001394325.1:p.Leu51Pro	missense
NM_001407397.1:c.152T>C	NP_001394326.1:p.Leu51Pro	missense
NM_001407398.1:c.152T>C	NP_001394327.1:p.Leu51Pro	missense
NM_001407399.1:c.152T>C	NP_001394328.1:p.Leu51Pro	missense
NM_001407400.1:c.152T>C	NP_001394329.1:p.Leu51Pro	missense
NM_001407401.1:c.152T>C	NP_001394330.1:p.Leu51Pro	missense
NC_000003.12:g.15635591T>C
NC_000003.11:g.15677098T>C
NG_008019.2:g.39240T>C

... more HGVS ... less HGVS

Protein change

L51P

Other names

L71P

Canonical SPDI

NC_000003.12:15635590:T:C

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.

0.00180 (C)

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

The Genome Aggregation Database (gnomAD) 0.00000

Trans-Omics for Precision Medicine (TOPMed) 0.00005

The Genome Aggregation Database (gnomAD), exomes 0.00154

1000 Genomes Project 30x 0.00156

Exome Aggregation Consortium (ExAC) 0.00159

1000 Genomes Project 0.00180

Links

ClinGen: CA278161 dbSNP: rs397514333 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.
BTD		-	-	GRCh38 GRCh37	669	755

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.
Biotinidase deficiency	Benign/Likely benign (4)	criteria provided, multiple submitters, no conflicts	Jan 11, 2024	RCV000021900.15
not specified	Conflicting interpretations of pathogenicity (2)	criteria provided, conflicting classifications	Nov 9, 2016	RCV000427971.8

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.
Uncertain significance (Nov 12, 2015)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not specified Affected status: no Allele origin: germline	Genetic Services Laboratory, University of Chicago Accession: SCV000593787.1 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017
Likely benign (Nov 09, 2016)	criteria provided, single submitter (GeneDx Variant Classification (06012015)) Method: clinical testing	not specified Affected status: yes Allele origin: germline	GeneDx Accession: SCV000521147.4 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017	Comment: This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more) This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
Likely benign (Apr 20, 2018)	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018)) Method: clinical testing	Biotinidase deficiency Affected status: unknown Allele origin: unknown	Counsyl Accession: SCV000800810.1 First in ClinVar: May 30, 2018 Last updated: May 30, 2018	Publications: PubMed (4) PubMed: 17185019‚ 15776412‚ 20083419‚ 14707518
Benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: research	Biotinidase deficiency (Autosomal recessive inheritance) Affected status: yes Allele origin: germline	Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard Accession: SCV001435233.1 First in ClinVar: Oct 02, 2020 Last updated: Oct 02, 2020	Publications: PubMed (1) PubMed: 14707518 Comment: The heterozygous p.Leu71Pro variant in BTD has been identified in the compound heterozygous state, in trans with a frameshift variant and in cis with a … (more) The heterozygous p.Leu71Pro variant in BTD has been identified in the compound heterozygous state, in trans with a frameshift variant and in cis with a rare missense variant, in an individual from Hungary with biotinidase deficiency (PMID: 14707518). This variant has also been identified in >1% of South Asian chromosomes and 8 homozygotes by ExAC (http://gnomad.broadinstitute.org/). In summary, this variant meets criteria to be classified as benign for autosomal recessive biotinidase deficiency. (less)
Benign (Jan 11, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Biotinidase deficiency Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000754950.5 First in ClinVar: Apr 04, 2013 Last updated: Feb 20, 2024
Benign (Jan 14, 2020)	no assertion criteria provided Method: clinical testing	Biotinidase deficiency Affected status: unknown Allele origin: germline	Natera, Inc. Accession: SCV002081544.1 First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022

Comment:

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

Comment:

The heterozygous p.Leu71Pro variant in BTD has been identified in the compound heterozygous state, in trans with a frameshift variant and in cis with a rare missense variant, in an individual from Hungary with biotinidase deficiency (PMID: 14707518). This variant has also been identified in >1% of South Asian chromosomes and 8 homozygotes by ExAC (http://gnomad.broadinstitute.org/). In summary, this variant meets criteria to be classified as benign for autosomal recessive biotinidase deficiency.

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
The identification of novel mutations in the biotinidase gene using denaturing high pressure liquid chromatography (dHPLC).	Iqbal F	Molecular genetics and metabolism	2010	PMID: 20083419
Mutations causing biotinidase deficiency in children ascertained by newborn screening in Western Hungary.	Milánkovics I	Molecular genetics and metabolism	2007	PMID: 17185019
Biotinidase deficiency: novel mutations and their biochemical and clinical correlates.	Wolf B	Human mutation	2005	PMID: 15776412
Neonatal screening for biotinidase deficiency in Hungary: clinical, biochemical and molecular studies.	László A	Journal of inherited metabolic disease	2003	PMID: 14707518

Text-mined citations for rs397514333 ...

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 Oct 08, 2024

ClinVar Genomic variation as it relates to human health

NM_001370658.1(BTD):c.152T>C (p.Leu51Pro)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs397514333 ...