19-5904919-G-T

Variant names:

• chr19-5904919-G-T
• rs781637600
• NM_001017921.4:c.29G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001017921.4(VMAC):​c.29G>T​(p.Arg10Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000149 in 1,338,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R10Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: VMAC NM_001017921.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.77
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39499676).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VMAC	NM_001017921.4	c.29G>T	p.Arg10Leu	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.29G>T	p.Arg10Leu	missense_variant	Exon 1 of 2	1	NM_001017921.4	ENSP00000343348.2
ENSG00000267314	ENST00000588891.1	n.29G>T		non_coding_transcript_exon_variant	Exon 1 of 4	4		ENSP00000468419.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000149 AC: 2 AN: 1338186 Hom.: 0 Cov.: 31 AF XY: 0.00000151 AC XY: 1 AN XY: 660884

African (AFR) AF: 0.00 AC: 0 AN: 27024

American (AMR) AF: 0.00 AC: 0 AN: 28278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23484

East Asian (EAS) AF: 0.00 AC: 0 AN: 29638

South Asian (SAS) AF: 0.00 AC: 0 AN: 74368

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33206

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

European-Non Finnish (NFE) AF: 9.41e-7 AC: 1 AN: 1062730

Other (OTH) AF: 0.0000180 AC: 1 AN: 55520

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Uncertain	0.063	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.071	D
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-0.59	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		2.8
PrimateAI	Pathogenic	0.87	D
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.27
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.015	D
Polyphen		1.0	D
Vest4		0.40
MutPred		0.26		Loss of MoRF binding (P = 0.014);
MVP		0.31
MPC		1.5
ClinPred		0.99	D
GERP RS		4.5
PromoterAI		-0.20	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.24
gMVP		0.28
Mutation Taster		=67/33	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: rs781637600; hg19: chr19-5904930;