rs746783531

Variant names:

• chr19-54040965-A-G
• NM_198481.4:c.707T>C

Your query was ambiguous. Multiple possible variants found:

• chr19-54040965-A-G
• chr19-54040965-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_198481.4(VSTM1):​c.707T>C​(p.Val236Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,457,180 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: VSTM1 NM_198481.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45

Genes affected

VSTM1 (HGNC:29455): (V-set and transmembrane domain containing 1) Predicted to enable cytokine activity. Predicted to be involved in immune system process and signal transduction. Predicted to be located in extracellular space. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06600675).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VSTM1	NM_198481.4	c.707T>C	p.Val236Ala	missense_variant	Exon 9 of 9	ENST00000338372.7	NP_940883.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VSTM1	ENST00000338372.7	c.707T>C	p.Val236Ala	missense_variant	Exon 9 of 9	1	NM_198481.4	ENSP00000343366.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1457180 Hom.: 0 Cov.: 34 AF XY: 0.00000276 AC XY: 2 AN XY: 724996

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: 0.00000180

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	12
DANN	Benign	0.97
DEOGEN2	Benign	0.0017	.;T;.;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0049	N
LIST_S2	Benign	0.45	T;.;.;.
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.066	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	.;L;.;.
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.2	N;N;N;N
REVEL	Benign	0.13
Sift	Pathogenic	0.0	D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		0.0060	.;B;.;.
Vest4		0.075, 0.080, 0.11
MutPred		0.23		.;Loss of sheet (P = 0.0228);.;.;
MVP		0.055
MPC		0.34
ClinPred		0.15	T
GERP RS		-4.2
Varity_R		0.042
gMVP		0.094

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-54544219;