Variant rs552113529 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP6

The NM_033305.3(VPS13A):c.7047G>A(p.Glu2349=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000292 in 1,607,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

VPS13A
NM_033305.3 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 1.31

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 9-77344173-G-A is Benign according to our data. Variant chr9-77344173-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 586933.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
VPS13A	NM_033305.3 linkuse as main transcript	c.7047G>A	p.Glu2349=	synonymous_variant	51/72	ENST00000360280.8	NP_150648.2
VPS13A	NM_001018037.2 linkuse as main transcript	c.6930G>A	p.Glu2310=	synonymous_variant	50/71		NP_001018047.1
VPS13A	NM_015186.4 linkuse as main transcript	c.7047G>A	p.Glu2349=	synonymous_variant	51/69		NP_056001.1
VPS13A	NM_001018038.3 linkuse as main transcript	c.7047G>A	p.Glu2349=	synonymous_variant	51/69		NP_001018048.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VPS13A	ENST00000360280.8 linkuse as main transcript	c.7047G>A	p.Glu2349=	synonymous_variant	51/72	1	NM_033305.3	ENSP00000353422	P4	Q96RL7-1
VPS13A	ENST00000376636.7 linkuse as main transcript	c.6930G>A	p.Glu2310=	synonymous_variant	50/71	1		ENSP00000365823		Q96RL7-3
VPS13A	ENST00000643348.1 linkuse as main transcript	c.7047G>A	p.Glu2349=	synonymous_variant	51/69			ENSP00000493592		Q96RL7-2
VPS13A	ENST00000645632.1 linkuse as main transcript	c.7047G>A	p.Glu2349=	synonymous_variant	51/69			ENSP00000496361	A1	Q96RL7-4

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152022

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000597

AC:

AN:

251308

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.000679

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000172

AC:

AN:

1455546

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

724528

show subpopulations

Gnomad4 AFR exome

AF:

0.000510

Gnomad4 AMR exome

AF:

0.0000895

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000665

GnomAD4 genome

AF:

0.000145

AC:

AN:

152140

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.000506

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000135

Hom.:

Bravo

AF:

0.000208

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 10, 2024	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Athena Diagnostics	Aug 20, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.22

Position offset: 12

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