Variant 19-5905080-C-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.190C>T(p.Arg64Cys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000272 in 1,351,726 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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: 𝑓 0.00019 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00028 ( 0 hom. )

Consequence

VMAC
NM_001017921.4 missense, splice_region

Scores

Splicing: ADA: 0.0007947

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.228

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=0.057291657).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VMAC	NM_001017921.4 linkuse as main transcript	c.190C>T	p.Arg64Cys	missense_variant, splice_region_variant	1/2	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.190C>T	p.Arg64Cys	missense_variant, splice_region_variant	1/2	1	NM_001017921.4	ENSP00000343348	P1

Frequencies

GnomAD3 genomes

AF:

0.000191

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000452

AC:

AN:

2212

Hom.:

AF XY:

0.00

AC XY:

AN XY:

1344

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:

0.000700

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000282

AC:

338

AN:

1199544

Hom.:

Cov.:

AF XY:

0.000277

AC XY:

161

AN XY:

580482

show subpopulations

Gnomad4 AFR exome

AF:

0.0000422

Gnomad4 AMR exome

AF:

0.000659

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000282

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000309

Gnomad4 OTH exome

AF:

0.000223

GnomAD4 genome

AF:

0.000191

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000347

Hom.:

Bravo

AF:

0.000215

ExAC

AF:

0.0000259

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

Mar 12, 2024

The c.190C>T (p.R64C) alteration is located in exon 1 (coding exon 1) of the VMAC gene. This alteration results from a C to T substitution at nucleotide position 190, causing the arginine (R) at amino acid position 64 to be replaced by a cysteine (C). 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

0.11

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.71

M_CAP

Benign

0.050

MetaRNN

Benign

0.057

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

MutationTaster

Benign

1.0

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.035

Sift

Benign

0.10

Sift4G

Benign

0.10

Polyphen

0.0060

Vest4

0.24

MutPred

0.24

Loss of MoRF binding (P = 0.038);

MVP

0.10

MPC

0.63

ClinPred

0.22

GERP RS

2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.11

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00079

dbscSNV1_RF

Benign

0.044

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