rs571818716

Variant names:

• chr19-5905018-G-A
• rs571818716
• NM_001017921.4:c.128G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-5905018-G-A
• chr19-5905018-G-C
• chr19-5905018-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001017921.4(VMAC):​c.128G>A​(p.Arg43His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000159 in 1,258,942 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R43L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: VMAC NM_001017921.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.87
• Publications: 0 publications found

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]

ENSG00000267314 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17978606).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VMAC	NM_001017921.4	c.128G>A	p.Arg43His	missense_variant	Exon 1 of 2	ENST00000339485.4	NP_001017921.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VMAC	ENST00000339485.4	c.128G>A	p.Arg43His	missense_variant	Exon 1 of 2	1	NM_001017921.4	ENSP00000343348.2
ENSG00000267314	ENST00000588891.1	n.128G>A		non_coding_transcript_exon_variant	Exon 1 of 4	4		ENSP00000468419.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000159 AC: 2 AN: 1258942 Hom.: 0 Cov.: 31 AF XY: 0.00000324 AC XY: 2 AN XY: 617362

African (AFR) AF: 0.00 AC: 0 AN: 24754

American (AMR) AF: 0.00 AC: 0 AN: 14504

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19802

East Asian (EAS) AF: 0.00 AC: 0 AN: 27712

South Asian (SAS) AF: 0.0000325 AC: 2 AN: 61552

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31216

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3824

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1023556

Other (OTH) AF: 0.00 AC: 0 AN: 52022

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.076	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.019	T
Eigen	Benign	0.12
Eigen_PC	Benign	0.037
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.56	T
M_CAP	Uncertain	0.085	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		2.9
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.057
Sift	Benign	0.065	T
Sift4G	Benign	0.11	T
Polyphen		0.99	D
Vest4		0.19
MutPred		0.20		Loss of MoRF binding (P = 0.0442);
MVP		0.15
MPC		0.59
ClinPred		0.72	D
GERP RS		2.4
PromoterAI		-0.13	Neutral
Varity_R		0.041
gMVP		0.12
Mutation Taster		=81/19	polymorphism

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

Other links and lift over

dbSNP: rs571818716; hg19: chr19-5905029;