10-49048493-C-G

Variant names:

• chr10-49048493-C-G
• rs753977306
• NM_001031746.5:c.760G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001031746.5(VSTM4):​c.760G>C​(p.Ala254Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000694 in 1,441,034 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: VSTM4 NM_001031746.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.45

Genes affected

VSTM4 (HGNC:26470): (V-set and transmembrane domain containing 4) Predicted to act upstream of or within several processes, including endothelial cell migration; retina blood vessel maintenance; and vasculature development. Predicted to be located in extracellular region and plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 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
VSTM4	NM_001031746.5	c.760G>C	p.Ala254Pro	missense_variant	Exon 6 of 8	ENST00000332853.9	NP_001026916.2
VSTM4	XM_017015827.3	c.760G>C	p.Ala254Pro	missense_variant	Exon 6 of 9		XP_016871316.1
VSTM4	XM_047424711.1	c.760G>C	p.Ala254Pro	missense_variant	Exon 6 of 9		XP_047280667.1
VSTM4	XR_001747052.3	n.797G>C		non_coding_transcript_exon_variant	Exon 6 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VSTM4	ENST00000332853.9	c.760G>C	p.Ala254Pro	missense_variant	Exon 6 of 8	1	NM_001031746.5	ENSP00000331062.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000432 AC: 1 AN: 231544 Hom.: 0 AF XY: 0.00000798 AC XY: 1 AN XY: 125280

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: 0.00000926

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.94e-7 AC: 1 AN: 1441034 Hom.: 0 Cov.: 31 AF XY: 0.00000140 AC XY: 1 AN XY: 716394

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.05e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.013	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0018	T
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.23
Sift	Benign	0.20	T
Sift4G	Benign	0.19	T
Polyphen		0.99	D
Vest4		0.59
MutPred		0.12		Gain of glycosylation at A254 (P = 0.0595);
MVP		0.48
MPC		0.68
ClinPred		0.78	D
GERP RS		6.2
Varity_R		0.32
gMVP		0.23

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

Other links and lift over

dbSNP: rs753977306; hg19: chr10-50256538;