NM_198481.4:c.209A>G

Variant names:

• chr19-54058452-T-C
• NM_198481.4:c.209A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_198481.4(VSTM1):​c.209A>G​(p.Gln70Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: VSTM1 NM_198481.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.00
• Publications: 0 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05148998).

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.209A>G	p.Gln70Arg	missense	Exon 3 of 9	NP_940883.2	Q6UX27-1
	VSTM1	NM_001288792.2		c.209A>G	p.Gln70Arg	missense	Exon 3 of 8	NP_001275721.1	Q6UX27-2
	VSTM1	NM_001288791.2		c.15+245A>G		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.209A>G	p.Gln70Arg	missense	Exon 3 of 9	ENSP00000343366.2	Q6UX27-1
	VSTM1	ENST00000376626.5	TSL:1	c.209A>G	p.Gln70Arg	missense	Exon 3 of 8	ENSP00000365813.1	Q6UX27-2
	VSTM1	ENST00000366170.6	TSL:1	c.34+5292A>G		intron	N/A	ENSP00000444153.2	D2DJS5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 31

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	0.078
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.24
DANN	Benign	0.32
DEOGEN2	Benign	0.0024	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.58	N
PhyloP100		-1.0
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-0.96	N
REVEL	Benign	0.0030
Sift	Benign	0.82	T
Sift4G	Benign	0.53	T
Polyphen		0.0	B
Vest4		0.033
MutPred		0.25		Gain of MoRF binding (P = 0.0503)
MVP		0.048
MPC		0.11
ClinPred		0.031	T
GERP RS		-2.9
PromoterAI		-0.035	Neutral
Varity_R		0.027
gMVP		0.24
Mutation Taster		=96/4	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

hg19: chr19-54561706;