19-54042298-T-C

Variant names:

• chr19-54042298-T-C
• NM_198481.4:c.466A>G

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.466A>G​(p.Ile156Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,872 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: 28)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: VSTM1 NM_198481.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.117
• 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=0.15520722).

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.466A>G	p.Ile156Val	missense	Exon 5 of 9	NP_940883.2	Q6UX27-1
	VSTM1	NM_001288791.2		c.202A>G	p.Ile68Val	missense	Exon 5 of 9	NP_001275720.1
	VSTM1	NM_001288793.2		c.106A>G	p.Ile36Val	missense	Exon 2 of 6	NP_001275722.1	D2DJS5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VSTM1	ENST00000338372.7	TSL:1 MANE Select	c.466A>G	p.Ile156Val	missense	Exon 5 of 9	ENSP00000343366.2	Q6UX27-1
	VSTM1	ENST00000366170.6	TSL:1	c.106A>G	p.Ile36Val	missense	Exon 2 of 6	ENSP00000444153.2	D2DJS5
	VSTM1	ENST00000376626.5	TSL:1	c.395-102A>G		intron	N/A	ENSP00000365813.1	Q6UX27-2

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461872 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 727234

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

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

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111996

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 28

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	0.18
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0046	T
Eigen	Benign	-0.022
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.22	N
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PhyloP100		0.12
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.21	N
REVEL	Benign	0.070
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.083	T
Polyphen		1.0	D
Vest4		0.10
MutPred		0.40		Gain of sheet (P = 0.0827)
MVP		0.12
MPC		0.47
ClinPred		0.78	D
GERP RS		3.6
Varity_R		0.13
gMVP		0.034
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

hg19: chr19-54545552;