19-54063758-G-A

Variant names:

• chr19-54063758-G-A
• rs199504672
• NM_198481.4:c.20C>T

Variant summary

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

The NM_198481.4(VSTM1):​c.20C>T​(p.Ser7Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000209 in 1,613,904 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00022 (0 hom.)
• Consequence: VSTM1 NM_198481.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.270
• Publications: 3 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=0.13984707).

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.20C>T	p.Ser7Phe	missense	Exon 1 of 9	NP_940883.2	Q6UX27-1
	VSTM1	NM_001288792.2		c.20C>T	p.Ser7Phe	missense	Exon 1 of 8	NP_001275721.1	Q6UX27-2
	VSTM1	NM_001288793.2		c.20C>T	p.Ser7Phe	missense	Exon 1 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.20C>T	p.Ser7Phe	missense	Exon 1 of 9	ENSP00000343366.2	Q6UX27-1
	VSTM1	ENST00000376626.5	TSL:1	c.20C>T	p.Ser7Phe	missense	Exon 1 of 8	ENSP00000365813.1	Q6UX27-2
	VSTM1	ENST00000366170.6	TSL:1	c.20C>T	p.Ser7Phe	missense	Exon 1 of 6	ENSP00000444153.2	D2DJS5

Frequencies

GnomAD3 genomes AF: 0.0000788 AC: 12 AN: 152220 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: 0.000176

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000599 AC: 15 AN: 250276 AF XY: 0.0000517

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000115

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000223 AC: 326 AN: 1461566 Hom.: 0 Cov.: 31 AF XY: 0.000204 AC XY: 148 AN XY: 727062

African (AFR) AF: 0.0000299 AC: 1 AN: 33460

American (AMR) AF: 0.00 AC: 0 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86168

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.000286 AC: 318 AN: 1111892

Other (OTH) AF: 0.0000994 AC: 6 AN: 60376

GnomAD4 genome AF: 0.0000788 AC: 12 AN: 152338 Hom.: 0 Cov.: 32 AF XY: 0.0000805 AC XY: 6 AN XY: 74494

African (AFR) AF: 0.00 AC: 0 AN: 41578

American (AMR) AF: 0.00 AC: 0 AN: 15304

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000148 Hom.: 0

Bravo AF: 0.0000604

ExAC AF: 0.0000330 AC: 4

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

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	0.17
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.012	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		-0.27
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.10
Sift	Benign	0.036	D
Sift4G	Benign	0.14	T
Polyphen		0.0060	B
Vest4		0.20
MVP		0.055
MPC		0.52
ClinPred		0.075	T
GERP RS		-3.7
PromoterAI		0.32	Neutral
Varity_R		0.054
gMVP		0.53
Mutation Taster		=93/7	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

dbSNP: rs199504672; hg19: chr19-54567012; COSMIC: COSV58075441;