rs7025532

Variant names:

• chr9-77339629-T-C
• rs7025532
• NM_033305.3:c.6492T>C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_033305.3(VPS13A):​c.6492T>C​(p.Asp2164Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 1,613,058 control chromosomes in the GnomAD database, including 30,275 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (2827 hom., cov: 31)
  • Exomes 𝑓: 0.19 (27448 hom.)
• Consequence: VPS13A NM_033305.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -0.102

Genes affected

VPS13A (HGNC:1908): (vacuolar protein sorting 13 homolog A) The protein encoded by this gene may control steps in the cycling of proteins through the trans-Golgi network to endosomes, lysosomes and the plasma membrane. Mutations in this gene cause the autosomal recessive disorder, chorea-acanthocytosis. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 9-77339629-T-C is Benign according to our data. Variant chr9-77339629-T-C is described in ClinVar as [Benign]. Clinvar id is 367402.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-77339629-T-C is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.102 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VPS13A	NM_033305.3	c.6492T>C	p.Asp2164Asp	synonymous_variant	Exon 48 of 72	ENST00000360280.8	NP_150648.2
VPS13A	NM_001018037.2	c.6375T>C	p.Asp2125Asp	synonymous_variant	Exon 47 of 71		NP_001018047.1
VPS13A	NM_015186.4	c.6492T>C	p.Asp2164Asp	synonymous_variant	Exon 48 of 69		NP_056001.1
VPS13A	NM_001018038.3	c.6492T>C	p.Asp2164Asp	synonymous_variant	Exon 48 of 69		NP_001018048.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VPS13A	ENST00000360280.8	c.6492T>C	p.Asp2164Asp	synonymous_variant	Exon 48 of 72	1	NM_033305.3	ENSP00000353422.3
VPS13A	ENST00000376636.7	c.6375T>C	p.Asp2125Asp	synonymous_variant	Exon 47 of 71	1		ENSP00000365823.3
VPS13A	ENST00000643348.1	c.6492T>C	p.Asp2164Asp	synonymous_variant	Exon 48 of 69			ENSP00000493592.1
VPS13A	ENST00000645632.1	c.6492T>C	p.Asp2164Asp	synonymous_variant	Exon 48 of 69			ENSP00000496361.1

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28388 AN: 151836 Hom.: 2823 Cov.: 31

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.0339

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.164

GnomAD3 exomes AF: 0.168 AC: 42021 AN: 250428 Hom.: 3969 AF XY: 0.173 AC XY: 23373 AN XY: 135286

Gnomad AFR exome AF: 0.217

Gnomad AMR exome AF: 0.0800

Gnomad ASJ exome AF: 0.178

Gnomad EAS exome AF: 0.0346

Gnomad SAS exome AF: 0.207

Gnomad FIN exome AF: 0.180

Gnomad NFE exome AF: 0.195

Gnomad OTH exome AF: 0.173

GnomAD4 exome AF: 0.189 AC: 275558 AN: 1461104 Hom.: 27448 Cov.: 36 AF XY: 0.189 AC XY: 137658 AN XY: 726794

Gnomad4 AFR exome AF: 0.223

Gnomad4 AMR exome AF: 0.0855

Gnomad4 ASJ exome AF: 0.176

Gnomad4 EAS exome AF: 0.0307

Gnomad4 SAS exome AF: 0.208

Gnomad4 FIN exome AF: 0.183

Gnomad4 NFE exome AF: 0.197

Gnomad4 OTH exome AF: 0.178

GnomAD4 genome AF: 0.187 AC: 28420 AN: 151954 Hom.: 2827 Cov.: 31 AF XY: 0.184 AC XY: 13666 AN XY: 74262

Gnomad4 AFR AF: 0.219

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.171

Gnomad4 EAS AF: 0.0340

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.177

Gnomad4 NFE AF: 0.194

Gnomad4 OTH AF: 0.162

Alfa AF: 0.190 Hom.: 5651

Bravo AF: 0.184

Asia WGS AF: 0.108 AC: 379 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Chorea-acanthocytosis Benign:4

Jul 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided Benign:4

Jul 17, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 07, 2018

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	6.5
DANN	Benign	0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7025532; hg19: chr9-79954545; COSMIC: COSV62430039; COSMIC: COSV62430039;