Variant 19-5909095-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001017921.4(VMAC):c.463G>T(p.Ala155Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000662 in 1,555,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000070 ( 0 hom. )

Consequence

VMAC
NM_001017921.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.18

Variant links:

Genes affected

VMAC (HGNC:33803): (vimentin type intermediate filament associated coiled-coil protein) Predicted to be located in cytoplasm. Predicted to be active in type III intermediate filament. [provided by Alliance of Genome Resources, Apr 2022]

VMAC links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.019619107).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VMAC	NM_001017921.4 linkuse as main transcript	c.463G>T	p.Ala155Ser	missense_variant	2/2	ENST00000339485.4	NP_001017921.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VMAC	ENST00000339485.4 linkuse as main transcript	c.463G>T	p.Ala155Ser	missense_variant	2/2	1	NM_001017921.4	ENSP00000343348	P1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000423

AC:

AN:

165458

Hom.:

AF XY:

0.0000672

AC XY:

AN XY:

89290

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:

0.000121

Gnomad NFE exome

AF:

0.0000844

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000698

AC:

AN:

1403650

Hom.:

Cov.:

AF XY:

0.0000777

AC XY:

AN XY:

694578

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:

0.0000255

Gnomad4 NFE exome

AF:

0.0000846

Gnomad4 OTH exome

AF:

0.0000855

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000122

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.00000850

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 14, 2023

The c.463G>T (p.A155S) alteration is located in exon 2 (coding exon 2) of the VMAC gene. This alteration results from a G to T substitution at nucleotide position 463, causing the alanine (A) at amino acid position 155 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.66

CADD

Benign

3.6

DANN

Benign

0.71

DEOGEN2

Benign

0.00061

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.34

M_CAP

Benign

0.0018

MetaRNN

Benign

0.020

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.20

MutationTaster

Benign

1.0

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.13

REVEL

Benign

0.071

Sift

Benign

0.72

Sift4G

Benign

0.72

Polyphen

0.0

Vest4

0.020

MutPred

0.042

Gain of phosphorylation at A155 (P = 0.0183);

MVP

0.014

MPC

0.42

ClinPred

0.025

GERP RS

1.0

Varity_R

0.030

gMVP

0.24

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