Variant chr9-77177524-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000376636.7(VPS13A):c.-181G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 604,510 control chromosomes in the GnomAD database, including 6,267 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1209 hom., cov: 33)

Exomes 𝑓: 0.14 ( 5058 hom. )

Consequence

VPS13A
ENST00000376636.7 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0420

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:

VPS13A-AS1 (HGNC:44167): (VPS13A antisense RNA 1)

VPS13A-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 9-77177524-G-A is Benign according to our data. Variant chr9-77177524-G-A is described in ClinVar as [Benign]. Clinvar id is 367338.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VPS13A-AS1	NR_026668.2 linkuse as main transcript	n.291+103C>T		intron_variant, non_coding_transcript_variant
VPS13A	NM_033305.3 linkuse as main transcript			upstream_gene_variant		ENST00000360280.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VPS13A-AS1	ENST00000644612.1 linkuse as main transcript	n.554+103C>T		intron_variant, non_coding_transcript_variant
VPS13A	ENST00000360280.8 linkuse as main transcript			upstream_gene_variant		1	NM_033305.3	P4	Q96RL7-1

Frequencies

GnomAD3 genomes

AF:

0.107

AC:

16332

AN:

152128

Hom.:

1207

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0295

Gnomad AMI

AF:

0.209

Gnomad AMR

AF:

0.0992

Gnomad ASJ

AF:

0.181

Gnomad EAS

AF:

0.00232

Gnomad SAS

AF:

0.167

Gnomad FIN

AF:

0.0896

Gnomad MID

AF:

0.205

Gnomad NFE

AF:

0.157

Gnomad OTH

AF:

0.132

GnomAD4 exome

AF:

0.137

AC:

62166

AN:

452266

Hom.:

5058

Cov.:

AF XY:

0.141

AC XY:

34207

AN XY:

242514

show subpopulations

Gnomad4 AFR exome

AF:

0.0276

Gnomad4 AMR exome

AF:

0.0807

Gnomad4 ASJ exome

AF:

0.186

Gnomad4 EAS exome

AF:

0.000391

Gnomad4 SAS exome

AF:

0.181

Gnomad4 FIN exome

AF:

0.101

Gnomad4 NFE exome

AF:

0.155

Gnomad4 OTH exome

AF:

0.135

GnomAD4 genome

AF:

0.107

AC:

16328

AN:

152244

Hom.:

1209

Cov.:

AF XY:

0.105

AC XY:

7821

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.0294

Gnomad4 AMR

AF:

0.0989

Gnomad4 ASJ

AF:

0.181

Gnomad4 EAS

AF:

0.00213

Gnomad4 SAS

AF:

0.168

Gnomad4 FIN

AF:

0.0896

Gnomad4 NFE

AF:

0.157

Gnomad4 OTH

AF:

0.130

Alfa

AF:

0.129

Hom.:

193

Bravo

AF:

0.103

Asia WGS

AF:

0.0690

AC:

241

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 14, 2018	- -

Chorea-acanthocytosis

Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

9.0

DANN

Benign

0.89

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