Variant 9-77177522-G-C 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.-183G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0981 in 599,262 control chromosomes in the GnomAD database, including 3,145 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 828 hom., cov: 33)

Exomes 𝑓: 0.097 ( 2317 hom. )

Consequence

VPS13A
ENST00000376636.7 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.100

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 9-77177522-G-C is Benign according to our data. Variant chr9-77177522-G-C is described in ClinVar as [Benign]. Clinvar id is 367337.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.108 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+105C>G		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+105C>G		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:

0.103

AC:

15592

AN:

152060

Hom.:

828

Cov.:

show subpopulations

Gnomad AFR

AF:

0.111

Gnomad AMI

AF:

0.0636

Gnomad AMR

AF:

0.0745

Gnomad ASJ

AF:

0.113

Gnomad EAS

AF:

0.0360

Gnomad SAS

AF:

0.0750

Gnomad FIN

AF:

0.124

Gnomad MID

AF:

0.131

Gnomad NFE

AF:

0.108

Gnomad OTH

AF:

0.0947

GnomAD4 exome

AF:

0.0966

AC:

43192

AN:

447084

Hom.:

2317

Cov.:

AF XY:

0.0961

AC XY:

23026

AN XY:

239622

show subpopulations

Gnomad4 AFR exome

AF:

0.111

Gnomad4 AMR exome

AF:

0.0522

Gnomad4 ASJ exome

AF:

0.105

Gnomad4 EAS exome

AF:

0.0346

Gnomad4 SAS exome

AF:

0.0802

Gnomad4 FIN exome

AF:

0.123

Gnomad4 NFE exome

AF:

0.107

Gnomad4 OTH exome

AF:

0.0948

GnomAD4 genome

AF:

0.103

AC:

15606

AN:

152178

Hom.:

828

Cov.:

AF XY:

0.102

AC XY:

7570

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.111

Gnomad4 AMR

AF:

0.0745

Gnomad4 ASJ

AF:

0.113

Gnomad4 EAS

AF:

0.0361

Gnomad4 SAS

AF:

0.0751

Gnomad4 FIN

AF:

0.124

Gnomad4 NFE

AF:

0.108

Gnomad4 OTH

AF:

0.0938

Alfa

AF:

0.0342

Hom.:

Bravo

AF:

0.0992

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	Jul 17, 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

-0.66

CADD

Benign

8.1

DANN

Benign

0.76

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

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