9-77323215-C-T

Position:

chr9-77323215-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_033305.3(VPS13A):c.5979C>T(p.Arg1993Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00823 in 1,613,050 control chromosomes in the GnomAD database, including 69 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0056 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0085 ( 66 hom. )

Consequence

VPS13A
NM_033305.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.339

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BP6

Variant 9-77323215-C-T is Benign according to our data. Variant chr9-77323215-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 448868.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-77323215-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.339 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00556 (846/152118) while in subpopulation NFE AF= 0.00992 (674/67952). AF 95% confidence interval is 0.0093. There are 3 homozygotes in gnomad4. There are 379 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VPS13A	NM_033305.3 linkuse as main transcript	c.5979C>T	p.Arg1993Arg	synonymous_variant	45/72	ENST00000360280.8	NP_150648.2	Q96RL7-1
VPS13A	NM_001018037.2 linkuse as main transcript	c.5862C>T	p.Arg1954Arg	synonymous_variant	44/71		NP_001018047.1	Q96RL7-3
VPS13A	NM_015186.4 linkuse as main transcript	c.5979C>T	p.Arg1993Arg	synonymous_variant	45/69		NP_056001.1	Q96RL7-2
VPS13A	NM_001018038.3 linkuse as main transcript	c.5979C>T	p.Arg1993Arg	synonymous_variant	45/69		NP_001018048.1	Q96RL7-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VPS13A	ENST00000360280.8 linkuse as main transcript	c.5979C>T	p.Arg1993Arg	synonymous_variant	45/72	1	NM_033305.3	ENSP00000353422.3		Q96RL7-1

Frequencies

GnomAD3 genomes

AF:

0.00557

AC:

846

AN:

152000

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00142

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00564

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00992

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00487

AC:

1221

AN:

250832

Hom.:

AF XY:

0.00485

AC XY:

658

AN XY:

135536

show subpopulations

Gnomad AFR exome

AF:

0.000985

Gnomad AMR exome

AF:

0.00200

Gnomad ASJ exome

AF:

0.00616

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00150

Gnomad FIN exome

AF:

0.000555

Gnomad NFE exome

AF:

0.00877

Gnomad OTH exome

AF:

0.00360

GnomAD4 exome

AF:

0.00851

AC:

12432

AN:

1460932

Hom.:

Cov.:

AF XY:

0.00810

AC XY:

5884

AN XY:

726798

show subpopulations

Gnomad4 AFR exome

AF:

0.00126

Gnomad4 AMR exome

AF:

0.00195

Gnomad4 ASJ exome

AF:

0.00621

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00123

Gnomad4 FIN exome

AF:

0.000656

Gnomad4 NFE exome

AF:

0.0105

Gnomad4 OTH exome

AF:

0.00481

GnomAD4 genome

AF:

0.00556

AC:

846

AN:

152118

Hom.:

Cov.:

AF XY:

0.00510

AC XY:

379

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.00142

Gnomad4 AMR

AF:

0.00564

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00992

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00651

Hom.:

Bravo

AF:

0.00502

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00835

EpiControl

AF:

0.00771

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 13, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	VPS13A: BP4, BP7, BS2 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 20, 2021	- -

Chorea-acanthocytosis

Benign:2

Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

VPS13A-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 02, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

6.7

DANN

Benign

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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