rs3737289

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_033305.3(VPS13A):c.9069A>G(p.Gly3023Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 1,613,544 control chromosomes in the GnomAD database, including 156,776 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 12981 hom., cov: 32)

Exomes 𝑓: 0.44 ( 143795 hom. )

Consequence

VPS13A
NM_033305.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.349

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=-0.5).

BP6

Variant 9-77371141-A-G is Benign according to our data. Variant chr9-77371141-A-G is described in ClinVar as [Benign]. Clinvar id is 367428.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-77371141-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.349 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VPS13A	NM_033305.3 link	c.9069A>G	p.Gly3023Gly	synonymous_variant	Exon 67 of 72	ENST00000360280.8	NP_150648.2	Q96RL7-1
VPS13A	NM_001018037.2 link	c.8952A>G	p.Gly2984Gly	synonymous_variant	Exon 66 of 71		NP_001018047.1	Q96RL7-3
VPS13A	NM_015186.4 link	c.9069A>G	p.Gly3023Gly	synonymous_variant	Exon 67 of 69		NP_056001.1	Q96RL7-2
VPS13A	NM_001018038.3 link	c.9069A>G	p.Gly3023Gly	synonymous_variant	Exon 67 of 69		NP_001018048.1	Q96RL7-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
VPS13A	ENST00000360280.8 link	c.9069A>G	p.Gly3023Gly	synonymous_variant	Exon 67 of 72	1	NM_033305.3	ENSP00000353422.3	Q96RL7-1
VPS13A	ENST00000376636.7 link	c.8952A>G	p.Gly2984Gly	synonymous_variant	Exon 66 of 71	1		ENSP00000365823.3	Q96RL7-3
VPS13A	ENST00000643348.1 link	c.9069A>G	p.Gly3023Gly	synonymous_variant	Exon 67 of 69			ENSP00000493592.1	Q96RL7-2
VPS13A	ENST00000645632.1 link	c.9069A>G	p.Gly3023Gly	synonymous_variant	Exon 67 of 69			ENSP00000496361.1	Q96RL7-4

Frequencies

GnomAD3 genomes

AF:

0.408

AC:

61972

AN:

151926

Hom.:

12970

Cov.:

show subpopulations

Gnomad AFR

AF:

0.319

Gnomad AMI

AF:

0.458

Gnomad AMR

AF:

0.490

Gnomad ASJ

AF:

0.399

Gnomad EAS

AF:

0.365

Gnomad SAS

AF:

0.525

Gnomad FIN

AF:

0.448

Gnomad MID

AF:

0.434

Gnomad NFE

AF:

0.432

Gnomad OTH

AF:

0.398

GnomAD3 exomes

AF:

0.454

AC:

113950

AN:

250736

Hom.:

26527

AF XY:

0.456

AC XY:

61851

AN XY:

135560

show subpopulations

Gnomad AFR exome

AF:

0.314

Gnomad AMR exome

AF:

0.576

Gnomad ASJ exome

AF:

0.414

Gnomad EAS exome

AF:

0.374

Gnomad SAS exome

AF:

0.542

Gnomad FIN exome

AF:

0.447

Gnomad NFE exome

AF:

0.433

Gnomad OTH exome

AF:

0.441

GnomAD4 exome

AF:

0.441

AC:

643904

AN:

1461500

Hom.:

143795

Cov.:

AF XY:

0.443

AC XY:

321733

AN XY:

727056

show subpopulations

Gnomad4 AFR exome

AF:

0.315

Gnomad4 AMR exome

AF:

0.558

Gnomad4 ASJ exome

AF:

0.413

Gnomad4 EAS exome

AF:

0.339

Gnomad4 SAS exome

AF:

0.536

Gnomad4 FIN exome

AF:

0.449

Gnomad4 NFE exome

AF:

0.437

Gnomad4 OTH exome

AF:

0.425

GnomAD4 genome

AF:

0.408

AC:

62012

AN:

152044

Hom.:

12981

Cov.:

AF XY:

0.411

AC XY:

30571

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.319

Gnomad4 AMR

AF:

0.490

Gnomad4 ASJ

AF:

0.399

Gnomad4 EAS

AF:

0.365

Gnomad4 SAS

AF:

0.525

Gnomad4 FIN

AF:

0.448

Gnomad4 NFE

AF:

0.432

Gnomad4 OTH

AF:

0.400

Alfa

AF:

0.420

Hom.:

25167

Bravo

AF:

0.406

Asia WGS

AF:

0.422

AC:

1467

AN:

3478

EpiCase

AF:

0.434

EpiControl

AF:

0.431

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Chorea-acanthocytosis

Benign:4

Jan 12, 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. -

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

- -

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 07, 2018

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 05, 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

- -

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

-0.50

CADD

Benign

5.2

DANN

Benign

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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