VCV002504637.4 - ClinVar

NM_015915.5(ATL1):c.1208G>C (p.Arg403Pro)

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.

(1)

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.

Likely pathogenic

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_015915.5(ATL1):c.1208G>C (p.Arg403Pro)

Variation ID: 2504637 Accession: VCV002504637.4

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 14q22.1 14: 50628119 (GRCh38) [ NCBI UCSC ] 14: 51094837 (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	Aug 19, 2023	May 26, 2024	May 22, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_015915.5:c.1208G>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_056999.2:p.Arg403Pro	missense
NM_001127713.1:c.1208G>C	NP_001121185.1:p.Arg403Pro	missense
NM_181598.4:c.1208G>C	NP_853629.2:p.Arg403Pro	missense
NC_000014.9:g.50628119G>C
NC_000014.8:g.51094837G>C
NG_009028.1:g.100038G>C
LRG_360:g.100038G>C
LRG_360t1:c.1208G>C	LRG_360p1:p.Arg403Pro
LRG_360t2:c.1208G>C	LRG_360p2:p.Arg403Pro

... more HGVS ... less HGVS

Protein change

R403P

Other names

Canonical SPDI

NC_000014.9:50628118:G: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.

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

Links

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.
ATL1		-	-	GRCh38 GRCh37	558	595

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.
Hereditary spastic paraplegia 3A	Likely pathogenic (1)	criteria provided, single submitter	May 22, 2024	RCV003320400.3

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.
Likely pathogenic (May 22, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: research	Hereditary spastic paraplegia 3A (Autosomal dominant inheritance) Affected status: yes Allele origin: germline	Neurogenomics Lab, Neuroscience Institute, University Of Cape Town Accession: SCV003930335.2 First in ClinVar: Aug 19, 2023 Last updated: May 26, 2024	Publications: PubMed (3) PubMed: 37712079‚ 28396731‚ 30008475 Comment: PM2_supporting: This variant is absent from gnomAD v4.0 (adequate coverage >20x confirmed) and an internal database of 1074 control alleles. PP3_met: REVEL score is 0.725. … (more) PM2_supporting: This variant is absent from gnomAD v4.0 (adequate coverage >20x confirmed) and an internal database of 1074 control alleles. PP3_met: REVEL score is 0.725. PM1 met: variant occurs in exon 12 together with other pathogenic mutations (PMID 28396731). PM6_supporting: 0.5 points awarded for proband with phenotype consistent with gene but not highly specific and unconfirmed parental relationships (PMID 30008475). PS4_supporting: variant identified in 1 unrelated proband with consistent phenotype for disorder (PMID 30008475).Sequencing funded by the International Centre for Genomic Medicine in Neuromuscular Diseases (ICGNMD): https://www.ucl.ac.uk/genomic-medicine-neuromuscular-diseases/. (less) Number of individuals with the variant: 1 Sex: female Geographic origin: South Africa

Comment:

PM2_supporting: This variant is absent from gnomAD v4.0 (adequate coverage >20x confirmed) and an internal database of 1074 control alleles. PP3_met: REVEL score is 0.725. PM1 met: variant occurs in exon 12 together with other pathogenic mutations (PMID 28396731). PM6_supporting: 0.5 points awarded for proband with phenotype consistent with gene but not highly specific and unconfirmed parental relationships (PMID 30008475). PS4_supporting: variant identified in 1 unrelated proband with consistent phenotype for disorder (PMID 30008475).Sequencing funded by the International Centre for Genomic Medicine in Neuromuscular Diseases (ICGNMD): https://www.ucl.ac.uk/genomic-medicine-neuromuscular-diseases/.

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 mutational profile in a South African cohort with inherited neuropathies and spastic paraplegia.	Mahungu AC	Frontiers in neurology	2023	PMID: 37712079
Clinical genome sequencing in an unbiased pediatric cohort.	Thiffault I	Genetics in medicine : official journal of the American College of Medical Genetics	2019	PMID: 30008475
Clinical features and genotype-phenotype correlation analysis in patients with ATL1 mutations: A literature reanalysis.	Zhao GH	Translational neurodegeneration	2017	PMID: 28396731

Text-mined citations for this variant ...

Record last updated Jun 02, 2024

ClinVar Genomic variation as it relates to human health

NM_015915.5(ATL1):c.1208G>C (p.Arg403Pro)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...