Variant 9-77228167-G-C 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.1498G>C(p.Val500Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000249 in 1,604,066 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

VPS13A
NM_033305.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.932

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=0.10757336).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
VPS13A	NM_033305.3 linkuse as main transcript	c.1498G>C	p.Val500Leu	missense_variant	17/72	ENST00000360280.8	NP_150648.2
VPS13A	NM_001018037.2 linkuse as main transcript	c.1498G>C	p.Val500Leu	missense_variant	17/71		NP_001018047.1
VPS13A	NM_015186.4 linkuse as main transcript	c.1498G>C	p.Val500Leu	missense_variant	17/69		NP_056001.1
VPS13A	NM_001018038.3 linkuse as main transcript	c.1498G>C	p.Val500Leu	missense_variant	17/69		NP_001018048.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VPS13A	ENST00000360280.8 linkuse as main transcript	c.1498G>C	p.Val500Leu	missense_variant	17/72	1	NM_033305.3	ENSP00000353422	P4	Q96RL7-1
VPS13A	ENST00000376636.7 linkuse as main transcript	c.1498G>C	p.Val500Leu	missense_variant	17/71	1		ENSP00000365823		Q96RL7-3
VPS13A	ENST00000643348.1 linkuse as main transcript	c.1498G>C	p.Val500Leu	missense_variant	17/69			ENSP00000493592		Q96RL7-2
VPS13A	ENST00000645632.1 linkuse as main transcript	c.1498G>C	p.Val500Leu	missense_variant	17/69			ENSP00000496361	A1	Q96RL7-4

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151908

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000657

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:

0.0000124

AC:

AN:

242574

Hom.:

AF XY:

0.0000229

AC XY:

AN XY:

131204

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000294

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000668

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000207

AC:

AN:

1452158

Hom.:

Cov.:

AF XY:

0.00000416

AC XY:

AN XY:

721904

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000226

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000235

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151908

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74188

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000657

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

ExAC

AF:

0.00000825

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.23

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

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.81

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

M_CAP

Benign

0.0077

MetaRNN

Benign

0.11

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

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

M;M;M;M;M;M;M

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.61

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

REVEL

Benign

0.014

Sift

Benign

0.22

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

Sift4G

Benign

0.12

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

Polyphen

0.038

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

Vest4

0.36

MutPred

0.38

Loss of catalytic residue at V500 (P = 0.0132);Loss of catalytic residue at V500 (P = 0.0132);Loss of catalytic residue at V500 (P = 0.0132);Loss of catalytic residue at V500 (P = 0.0132);Loss of catalytic residue at V500 (P = 0.0132);Loss of catalytic residue at V500 (P = 0.0132);Loss of catalytic residue at V500 (P = 0.0132);

MVP

0.40

MPC

0.13

ClinPred

0.13

GERP RS

2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.037

gMVP

0.36

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over