Variant rs749375820 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_033305.3(VPS13A):c.2288A>G(p.Lys763Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,454,180 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

VPS13A
NM_033305.3 missense, splice_region

Scores

Splicing: ADA: 0.001931

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.27

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13161203).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
VPS13A	NM_033305.3 linkuse as main transcript	c.2288A>G	p.Lys763Arg	missense_variant, splice_region_variant	22/72	ENST00000360280.8	NP_150648.2
VPS13A	NM_001018037.2 linkuse as main transcript	c.2288A>G	p.Lys763Arg	missense_variant, splice_region_variant	22/71		NP_001018047.1
VPS13A	NM_015186.4 linkuse as main transcript	c.2288A>G	p.Lys763Arg	missense_variant, splice_region_variant	22/69		NP_056001.1
VPS13A	NM_001018038.3 linkuse as main transcript	c.2288A>G	p.Lys763Arg	missense_variant, splice_region_variant	22/69		NP_001018048.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VPS13A	ENST00000360280.8 linkuse as main transcript	c.2288A>G	p.Lys763Arg	missense_variant, splice_region_variant	22/72	1	NM_033305.3	ENSP00000353422	P4	Q96RL7-1
VPS13A	ENST00000376636.7 linkuse as main transcript	c.2288A>G	p.Lys763Arg	missense_variant, splice_region_variant	22/71	1		ENSP00000365823		Q96RL7-3
VPS13A	ENST00000643348.1 linkuse as main transcript	c.2288A>G	p.Lys763Arg	missense_variant, splice_region_variant	22/69			ENSP00000493592		Q96RL7-2
VPS13A	ENST00000645632.1 linkuse as main transcript	c.2288A>G	p.Lys763Arg	missense_variant, splice_region_variant	22/69			ENSP00000496361	A1	Q96RL7-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251412

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1454180

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

724040

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000181

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Athena Diagnostics

Aug 20, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.16

.;.;T;.;.;.;T

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.19

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.84

.;T;.;.;T;T;T

M_CAP

Benign

0.052

MetaRNN

Benign

0.13

T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;L;L;L;L;L;L

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.83

N;N;N;N;.;.;.

REVEL

Benign

0.049

Sift

Benign

0.49

T;T;T;T;.;.;.

Sift4G

Benign

0.61

T;T;T;T;.;.;.

Polyphen

0.031

B;B;B;B;B;B;B

Vest4

0.20

MutPred

0.50

Loss of methylation at K763 (P = 0.0286);Loss of methylation at K763 (P = 0.0286);Loss of methylation at K763 (P = 0.0286);Loss of methylation at K763 (P = 0.0286);Loss of methylation at K763 (P = 0.0286);Loss of methylation at K763 (P = 0.0286);Loss of methylation at K763 (P = 0.0286);

MVP

0.66

MPC

0.11

ClinPred

0.29

GERP RS

3.1

Varity_R

0.048

gMVP

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0019

dbscSNV1_RF

Benign

0.090

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