19-5905047-G-C

Variant names:

• chr19-5905047-G-C
• rs1482110743
• NM_001017921.4:c.157G>C

Variant summary

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

The NM_001017921.4(VMAC):​c.157G>C​(p.Ala53Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000815 in 1,226,812 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A53S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 8.2e-7 (0 hom.)
• Consequence: VMAC NM_001017921.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.70
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VMAC	NM_001017921.4	c.157G>C	p.Ala53Pro	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.157G>C	p.Ala53Pro	missense_variant	Exon 1 of 2	1	NM_001017921.4	ENSP00000343348.2
ENSG00000267314	ENST00000588891.1	n.157G>C		non_coding_transcript_exon_variant	Exon 1 of 4	4		ENSP00000468419.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.15e-7 AC: 1 AN: 1226812 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 598138

African (AFR) AF: 0.00 AC: 0 AN: 24162

American (AMR) AF: 0.00 AC: 0 AN: 10676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17482

East Asian (EAS) AF: 0.0000363 AC: 1 AN: 27536

South Asian (SAS) AF: 0.00 AC: 0 AN: 54956

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29736

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3938

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1007766

Other (OTH) AF: 0.00 AC: 0 AN: 50560

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Uncertain	0.088	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.25
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.064	D
MetaRNN	Uncertain	0.57	D
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		4.7
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.23
Sift	Benign	0.090	T
Sift4G	Uncertain	0.025	D
Polyphen		0.99	D
Vest4		0.63
MutPred		0.21		Loss of MoRF binding (P = 0.0712);
MVP		0.34
MPC		1.5
ClinPred		0.98	D
GERP RS		3.3
PromoterAI		-0.10	Neutral
Varity_R		0.56
gMVP		0.53
Mutation Taster		=76/24	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: rs1482110743; hg19: chr19-5905058;