rs17340192

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_033305.3(VPS13A):c.8571T>C(p.Tyr2857Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.081 in 1,610,632 control chromosomes in the GnomAD database, including 6,011 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.060 ( 378 hom., cov: 33)

Exomes 𝑓: 0.083 ( 5633 hom. )

Consequence

VPS13A
NM_033305.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.30

Publications

8 publications found

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 Gene-Disease associations (from GenCC):

chorea-acanthocytosis
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae)

VPS13A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 9-77369316-T-C is Benign according to our data. Variant chr9-77369316-T-C is described in ClinVar as Benign. ClinVar VariationId is 367423.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VPS13A	NM_033305.3 link	c.8571T>C	p.Tyr2857Tyr	synonymous_variant	Exon 63 of 72	ENST00000360280.8	NP_150648.2	Q96RL7-1
VPS13A	NM_001018037.2 link	c.8454T>C	p.Tyr2818Tyr	synonymous_variant	Exon 62 of 71		NP_001018047.1	Q96RL7-3
VPS13A	NM_015186.4 link	c.8571T>C	p.Tyr2857Tyr	synonymous_variant	Exon 63 of 69		NP_056001.1	Q96RL7-2
VPS13A	NM_001018038.3 link	c.8571T>C	p.Tyr2857Tyr	synonymous_variant	Exon 63 of 69		NP_001018048.1	Q96RL7-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
VPS13A	ENST00000360280.8 link	c.8571T>C	p.Tyr2857Tyr	synonymous_variant	Exon 63 of 72	1	NM_033305.3	ENSP00000353422.3	Q96RL7-1
VPS13A	ENST00000376636.7 link	c.8454T>C	p.Tyr2818Tyr	synonymous_variant	Exon 62 of 71	1		ENSP00000365823.3	Q96RL7-3
VPS13A	ENST00000643348.1 link	c.8571T>C	p.Tyr2857Tyr	synonymous_variant	Exon 63 of 69			ENSP00000493592.1	Q96RL7-2
VPS13A	ENST00000645632.1 link	c.8571T>C	p.Tyr2857Tyr	synonymous_variant	Exon 63 of 69			ENSP00000496361.1	Q96RL7-4

Frequencies

GnomAD3 genomes

AF:

0.0600

AC:

9127

AN:

152178

Hom.:

377

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0242

Gnomad AMI

AF:

0.0439

Gnomad AMR

AF:

0.0473

Gnomad ASJ

AF:

0.0579

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.120

Gnomad FIN

AF:

0.0567

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.0854

Gnomad OTH

AF:

0.0578

GnomAD2 exomes

AF:

0.0721

AC:

18126

AN:

251378

AF XY:

0.0780

show subpopulations

Gnomad AFR exome

AF:

0.0252

Gnomad AMR exome

AF:

0.0304

Gnomad ASJ exome

AF:

0.0685

Gnomad EAS exome

AF:

0.000544

Gnomad FIN exome

AF:

0.0624

Gnomad NFE exome

AF:

0.0908

Gnomad OTH exome

AF:

0.0752

GnomAD4 exome

AF:

0.0832

AC:

121299

AN:

1458336

Hom.:

5633

Cov.:

AF XY:

0.0849

AC XY:

61639

AN XY:

725708

show subpopulations

African (AFR)

AF:

0.0207

AC:

692

AN:

33432

American (AMR)

AF:

0.0324

AC:

1451

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0693

AC:

1809

AN:

26100

East Asian (EAS)

AF:

0.000227

AC:

AN:

39608

South Asian (SAS)

AF:

0.126

AC:

10874

AN:

86182

European-Finnish (FIN)

AF:

0.0647

AC:

3458

AN:

53412

Middle Eastern (MID)

AF:

0.108

AC:

624

AN:

5764

European-Non Finnish (NFE)

AF:

0.0883

AC:

97921

AN:

1108838

Other (OTH)

AF:

0.0740

AC:

4461

AN:

60280

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

4908

9816

14724

19632

24540

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3582

7164

10746

14328

17910

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0599

AC:

9124

AN:

152296

Hom.:

378

Cov.:

AF XY:

0.0589

AC XY:

4387

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.0242

AC:

1004

AN:

41570

American (AMR)

AF:

0.0471

AC:

721

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0579

AC:

201

AN:

3470

East Asian (EAS)

AF:

0.00116

AC:

AN:

5188

South Asian (SAS)

AF:

0.121

AC:

583

AN:

4822

European-Finnish (FIN)

AF:

0.0567

AC:

602

AN:

10608

Middle Eastern (MID)

AF:

0.116

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0855

AC:

5813

AN:

68022

Other (OTH)

AF:

0.0568

AC:

120

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

443

886

1330

1773

2216

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

220

330

440

550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0740

Hom.:

398

Bravo

AF:

0.0566

Asia WGS

AF:

0.0490

AC:

171

AN:

3478

EpiCase

AF:

0.0845

EpiControl

AF:

0.0869

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Sep 04, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 02, 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

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Chorea-acanthocytosis

Benign:3

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. -

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jul 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

4.4

(source)

DANN

Benign

0.59

PhyloP100

1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over