Variant 19-5909038-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The ENST00000339485.4(VMAC):c.406G>A(p.Gly136Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000162 in 1,422,478 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 Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

VMAC
ENST00000339485.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B: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:

ENSG00000267314 (HGNC:):

ENSG00000267314 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.031132728).

BP6

Variant 19-5909038-G-A is Benign according to our data. Variant chr19-5909038-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3332108.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VMAC	NM_001017921.4 linkuse as main transcript	c.406G>A	p.Gly136Ser	missense_variant	2/2	ENST00000339485.4	NP_001017921.1	Q2NL98

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VMAC	ENST00000339485.4 linkuse as main transcript	c.406G>A	p.Gly136Ser	missense_variant	2/2	1	NM_001017921.4	ENSP00000343348.2		Q2NL98
ENSG00000267314	ENST00000588891.1 linkuse as main transcript	n.191+3957G>A		intron_variant		4		ENSP00000468419.1		K7ERU9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000168

AC:

AN:

179090

Hom.:

AF XY:

0.0000102

AC XY:

AN XY:

97692

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000765

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000162

AC:

AN:

1422478

Hom.:

Cov.:

AF XY:

0.0000156

AC XY:

AN XY:

705174

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000259

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000534

Gnomad4 SAS exome

AF:

0.0000121

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000165

Gnomad4 OTH exome

AF:

0.0000170

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000302

ExAC

AF:

0.00000849

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 04, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.031

DANN

Benign

0.47

DEOGEN2

Benign

0.0054

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.46

M_CAP

Benign

0.0028

MetaRNN

Benign

0.031

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.5

MutationTaster

Benign

1.0

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.57

REVEL

Benign

0.0080

Sift

Benign

0.40

Sift4G

Benign

0.74

Polyphen

0.0030

Vest4

0.062

MutPred

0.10

Gain of phosphorylation at G136 (P = 0.0056);

MVP

0.014

MPC

0.46

ClinPred

0.020

GERP RS

-1.6

Varity_R

0.030

gMVP

0.22

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