19-54063999-A-T

Variant names:

• chr19-54063999-A-T
• rs612529
• NM_198481.4:c.-222T>A

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.-222T>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 365,438 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: VSTM1 NM_198481.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 34 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 (BayesDel_noAF=-0.87).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VSTM1	NM_198481.4	MANE Select	c.-222T>A		upstream_gene	N/A	NP_940883.2
	VSTM1	NM_001288792.2		c.-222T>A		upstream_gene	N/A	NP_001275721.1
	VSTM1	NM_001288791.2		c.-277T>A		upstream_gene	N/A	NP_001275720.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VSTM1	ENST00000338372.7	TSL:1 MANE Select	c.-222T>A		upstream_gene	N/A	ENSP00000343366.2
	VSTM1	ENST00000376626.5	TSL:1	c.-222T>A		upstream_gene	N/A	ENSP00000365813.1
	VSTM1	ENST00000366170.6	TSL:1	c.-222T>A		upstream_gene	N/A	ENSP00000444153.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000274 AC: 1 AN: 365438 Hom.: 0 Cov.: 4 AF XY: 0.00 AC XY: 0 AN XY: 190684

African (AFR) AF: 0.00 AC: 0 AN: 8546

American (AMR) AF: 0.00 AC: 0 AN: 9454

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12016

East Asian (EAS) AF: 0.00 AC: 0 AN: 23968

South Asian (SAS) AF: 0.00 AC: 0 AN: 31334

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28052

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1702

European-Non Finnish (NFE) AF: 0.00000439 AC: 1 AN: 227990

Other (OTH) AF: 0.00 AC: 0 AN: 22376

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 12345

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.14
DANN	Benign	0.54
PhyloP100		-1.1
PromoterAI		0.12	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs612529; hg19: chr19-54567253;