19-54058468-C-A

Variant names:

• chr19-54058468-C-A
• rs144159930
• NM_198481.4:c.193G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_198481.4(VSTM1):​c.193G>T​(p.Asp65Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000682 in 1,613,894 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00042 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00071 (1 hom.)
• Consequence: VSTM1 NM_198481.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0460
• Publications: 7 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06485072).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198481.4. 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
	VSTM1	NM_198481.4	MANE Select	c.193G>T	p.Asp65Tyr	missense	Exon 3 of 9	NP_940883.2	Q6UX27-1
	VSTM1	NM_001288792.2		c.193G>T	p.Asp65Tyr	missense	Exon 3 of 8	NP_001275721.1	Q6UX27-2
	VSTM1	NM_001288791.2		c.15+229G>T		intron	N/A	NP_001275720.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VSTM1	ENST00000338372.7	TSL:1 MANE Select	c.193G>T	p.Asp65Tyr	missense	Exon 3 of 9	ENSP00000343366.2	Q6UX27-1
	VSTM1	ENST00000376626.5	TSL:1	c.193G>T	p.Asp65Tyr	missense	Exon 3 of 8	ENSP00000365813.1	Q6UX27-2
	VSTM1	ENST00000366170.6	TSL:1	c.34+5276G>T		intron	N/A	ENSP00000444153.2	D2DJS5

Frequencies

GnomAD3 genomes AF: 0.000421 AC: 64 AN: 152002 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000266

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000657

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000735

Gnomad OTH AF: 0.000958

GnomAD2 exomes AF: 0.000421 AC: 106 AN: 251492 AF XY: 0.000397

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.000844

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000709 AC: 1036 AN: 1461892 Hom.: 1 Cov.: 35 AF XY: 0.000679 AC XY: 494 AN XY: 727248

African (AFR) AF: 0.0000896 AC: 3 AN: 33480

American (AMR) AF: 0.0000671 AC: 3 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.000243 AC: 13 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000890 AC: 990 AN: 1112012

Other (OTH) AF: 0.000430 AC: 26 AN: 60396

GnomAD4 genome AF: 0.000421 AC: 64 AN: 152002 Hom.: 0 Cov.: 31 AF XY: 0.000337 AC XY: 25 AN XY: 74230

African (AFR) AF: 0.000266 AC: 11 AN: 41384

American (AMR) AF: 0.0000657 AC: 1 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000735 AC: 50 AN: 68006

Other (OTH) AF: 0.000958 AC: 2 AN: 2088

Alfa AF: 0.000710 Hom.: 0

Bravo AF: 0.000385

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.00130 AC: 5

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000698 AC: 6

ExAC AF: 0.000420 AC: 51

EpiCase AF: 0.000600

EpiControl AF: 0.000533

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	16
DANN	Benign	0.96
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		0.046
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.039
Sift	Benign	0.038	D
Sift4G	Benign	0.066	T
Polyphen		1.0	D
Vest4		0.38
MVP		0.095
MPC		0.57
ClinPred		0.061	T
GERP RS		-1.2
PromoterAI		-0.018	Neutral
Varity_R		0.075
gMVP		0.53
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs144159930; hg19: chr19-54561722;