chr19-54051441-G-C

Variant names:

• chr19-54051441-G-C
• rs373982331
• NM_198481.4:c.363C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_198481.4(VSTM1):​c.363C>G​(p.His121Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000277 in 1,441,480 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: VSTM1 NM_198481.4 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: -0.352
• 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.

• BP4: Computational evidence support a benign effect (MetaRNN=0.080476284).

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.363C>G	p.His121Gln	missense	Exon 4 of 9	NP_940883.2	Q6UX27-1
	VSTM1	NM_001288792.2		c.363C>G	p.His121Gln	missense	Exon 4 of 8	NP_001275721.1	Q6UX27-2
	VSTM1	NM_001288791.2		c.99C>G	p.His33Gln	missense	Exon 4 of 9	NP_001275720.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VSTM1	ENST00000338372.7	TSL:1 MANE Select	c.363C>G	p.His121Gln	missense	Exon 4 of 9	ENSP00000343366.2	Q6UX27-1
	VSTM1	ENST00000376626.5	TSL:1	c.363C>G	p.His121Gln	missense	Exon 4 of 8	ENSP00000365813.1	Q6UX27-2
	VSTM1	ENST00000366170.6	TSL:1	c.35-9072C>G		intron	N/A	ENSP00000444153.2	D2DJS5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000435 AC: 1 AN: 230046 AF XY: 0.00000798

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000925

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000277 AC: 4 AN: 1441480 Hom.: 0 Cov.: 30 AF XY: 0.00000279 AC XY: 2 AN XY: 717300

African (AFR) AF: 0.00 AC: 0 AN: 31716

American (AMR) AF: 0.00 AC: 0 AN: 38204

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25578

East Asian (EAS) AF: 0.00 AC: 0 AN: 38700

South Asian (SAS) AF: 0.00 AC: 0 AN: 82556

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53238

Middle Eastern (MID) AF: 0.000527 AC: 3 AN: 5698

European-Non Finnish (NFE) AF: 9.04e-7 AC: 1 AN: 1106162

Other (OTH) AF: 0.00 AC: 0 AN: 59628

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000225 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.16
DANN	Benign	0.40
DEOGEN2	Benign	0.0062	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0049	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
PhyloP100		-0.35
PrimateAI	Benign	0.25	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.016
Sift	Benign	0.031	D
Sift4G	Benign	0.57	T
Polyphen		0.018	B
Vest4		0.10
MutPred		0.40		Gain of solvent accessibility (P = 0.0338)
MVP		0.014
MPC		0.10
ClinPred		0.085	T
GERP RS		-4.6
Varity_R		0.060
gMVP		0.041
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs373982331; hg19: chr19-54554695;