19-54051441-G-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198481.4(VSTM1):​c.363C>A​(p.His121Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000251 in 1,593,596 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: VSTM1 NM_198481.4 missense
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07711777).

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>A	p.His121Gln	missense	Exon 4 of 9	NP_940883.2	Q6UX27-1
	VSTM1	NM_001288792.2		c.363C>A	p.His121Gln	missense	Exon 4 of 8	NP_001275721.1	Q6UX27-2
	VSTM1	NM_001288791.2		c.99C>A	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>A	p.His121Gln	missense	Exon 4 of 9	ENSP00000343366.2	Q6UX27-1
	VSTM1	ENST00000376626.5	TSL:1	c.363C>A	p.His121Gln	missense	Exon 4 of 8	ENSP00000365813.1	Q6UX27-2
	VSTM1	ENST00000366170.6	TSL:1	c.35-9072C>A		intron	N/A	ENSP00000444153.2	D2DJS5

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152116 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000208 AC: 3 AN: 1441480 Hom.: 0 Cov.: 30 AF XY: 0.00000139 AC XY: 1 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: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1106162

Other (OTH) AF: 0.0000168 AC: 1 AN: 59628

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152116 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74306

African (AFR) AF: 0.00 AC: 0 AN: 41422

American (AMR) AF: 0.00 AC: 0 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ClinVar

Not reported in ClinVar

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	0.12
DANN	Benign	0.39
DEOGEN2	Benign	0.0062	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0038	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.077	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	0.018
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)		0.010		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: rs373982331; hg19: chr19-54554695;