rs7025532

Positions:

chr9-77339629-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_033305.3(VPS13A):c.6492T>C(p.Asp2164=) 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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.102

Variant links:

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]

VPS13A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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/exons	MANE
VPS13A	NM_033305.3 linkuse as main transcript	c.6492T>C	p.Asp2164=	synonymous_variant	48/72	ENST00000360280.8
VPS13A	NM_001018037.2 linkuse as main transcript	c.6375T>C	p.Asp2125=	synonymous_variant	47/71
VPS13A	NM_015186.4 linkuse as main transcript	c.6492T>C	p.Asp2164=	synonymous_variant	48/69
VPS13A	NM_001018038.3 linkuse as main transcript	c.6492T>C	p.Asp2164=	synonymous_variant	48/69

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VPS13A	ENST00000360280.8 linkuse as main transcript	c.6492T>C	p.Asp2164=	synonymous_variant	48/72	1	NM_033305.3	P4	Q96RL7-1
VPS13A	ENST00000376636.7 linkuse as main transcript	c.6375T>C	p.Asp2125=	synonymous_variant	47/71	1			Q96RL7-3
VPS13A	ENST00000643348.1 linkuse as main transcript	c.6492T>C	p.Asp2164=	synonymous_variant	48/69				Q96RL7-2
VPS13A	ENST00000645632.1 linkuse as main transcript	c.6492T>C	p.Asp2164=	synonymous_variant	48/69			A1	Q96RL7-4

Frequencies

GnomAD3 genomes

AF:

0.187

AC:

28388

AN:

151836

Hom.:

2823

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.189

AC XY:

137658

AN XY:

726794

show subpopulations

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.:

AF XY:

0.184

AC XY:

13666

AN XY:

74262

show subpopulations

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:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Chorea-acanthocytosis

Benign:4

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 10, 2021	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 07, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 17, 2018	- -

not specified

Benign:1

Benign, no assertion criteria provided

clinical testing

Genome Diagnostics Laboratory, Amsterdam University Medical Center

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over