NM_001031746.5:c.203T>C

Variant names:

• chr10-49107848-A-G
• rs13088
• NM_001031746.5:c.203T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001031746.5(VSTM4):​c.203T>C​(p.Phe68Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 1,613,938 control chromosomes in the GnomAD database, including 142,856 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. F68F) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.48 (19390 hom., cov: 33)
  • Exomes 𝑓: 0.41 (123466 hom.)
• Consequence: VSTM4 NM_001031746.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.870
• Publications: 33 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.616328E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031746.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VSTM4	NM_001031746.5	MANE Select	c.203T>C	p.Phe68Ser	missense	Exon 2 of 8	NP_001026916.2	Q8IW00-1
	VSTM4	NM_144984.4		c.203T>C	p.Phe68Ser	missense	Exon 2 of 3	NP_659421.1	Q8IW00-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VSTM4	ENST00000332853.9	TSL:1 MANE Select	c.203T>C	p.Phe68Ser	missense	Exon 2 of 8	ENSP00000331062.3	Q8IW00-1
	VSTM4	ENST00000956395.1		c.203T>C	p.Phe68Ser	missense	Exon 2 of 9	ENSP00000626454.1
	VSTM4	ENST00000298454.3	TSL:2	c.203T>C	p.Phe68Ser	missense	Exon 2 of 3	ENSP00000298454.3	Q8IW00-2

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73668 AN: 151992 Hom.: 19362 Cov.: 33

Gnomad AFR AF: 0.704

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.475

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.463

GnomAD2 exomes AF: 0.423 AC: 106238 AN: 251230 AF XY: 0.420

Gnomad AFR exome AF: 0.710

Gnomad AMR exome AF: 0.446

Gnomad ASJ exome AF: 0.447

Gnomad EAS exome AF: 0.207

Gnomad FIN exome AF: 0.372

Gnomad NFE exome AF: 0.401

Gnomad OTH exome AF: 0.415

GnomAD4 exome AF: 0.405 AC: 592248 AN: 1461826 Hom.: 123466 Cov.: 90 AF XY: 0.407 AC XY: 295650 AN XY: 727208

African (AFR) AF: 0.714 AC: 23912 AN: 33480

American (AMR) AF: 0.446 AC: 19959 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.444 AC: 11592 AN: 26136

East Asian (EAS) AF: 0.220 AC: 8746 AN: 39698

South Asian (SAS) AF: 0.479 AC: 41304 AN: 86258

European-Finnish (FIN) AF: 0.376 AC: 20101 AN: 53404

Middle Eastern (MID) AF: 0.434 AC: 2506 AN: 5768

European-Non Finnish (NFE) AF: 0.395 AC: 439249 AN: 1111974

Other (OTH) AF: 0.412 AC: 24879 AN: 60396

GnomAD4 genome AF: 0.485 AC: 73753 AN: 152112 Hom.: 19390 Cov.: 33 AF XY: 0.483 AC XY: 35923 AN XY: 74354

African (AFR) AF: 0.704 AC: 29226 AN: 41512

American (AMR) AF: 0.466 AC: 7124 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 1559 AN: 3468

East Asian (EAS) AF: 0.219 AC: 1133 AN: 5164

South Asian (SAS) AF: 0.475 AC: 2291 AN: 4822

European-Finnish (FIN) AF: 0.366 AC: 3873 AN: 10574

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.398 AC: 27072 AN: 67966

Other (OTH) AF: 0.458 AC: 964 AN: 2106

Alfa AF: 0.426 Hom.: 49838

Bravo AF: 0.497

TwinsUK AF: 0.389 AC: 1441

ALSPAC AF: 0.394 AC: 1519

ESP6500AA AF: 0.708 AC: 3121

ESP6500EA AF: 0.393 AC: 3376

ExAC AF: 0.429 AC: 52136

Asia WGS AF: 0.396 AC: 1375 AN: 3478

EpiCase AF: 0.395

EpiControl AF: 0.405

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.032
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	4.4
DANN	Benign	0.22
DEOGEN2	Benign	0.0041	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0097	N
LIST_S2	Benign	0.26	T
MetaRNN	Benign	0.0000026	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.87
PrimateAI	Benign	0.30	T
PROVEAN	Benign	2.9	N
REVEL	Benign	0.043
Sift	Benign	0.97	T
Sift4G	Benign	0.77	T
Polyphen		0.0	B
Vest4		0.037
MPC		0.29
ClinPred		0.00051	T
GERP RS		1.8
Varity_R		0.025
gMVP		0.38
Mutation Taster		=99/1	polymorphism (auto)

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: rs13088; hg19: chr10-50315893; COSMIC: COSV53677992;