chr7-54553999-G-C

Variant names:

• chr7-54553999-G-C
• rs68106607
• NM_001301009.2:c.634+3829G>C

Variant summary

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

The NM_001301009.2(VSTM2A):​c.634+3829G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,928 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: 𝑓 0.0000066 (0 hom., cov: 31)
• Consequence: VSTM2A NM_001301009.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 3 publications found

Genes affected

VSTM2A (HGNC:28499): (V-set and transmembrane domain containing 2A) Predicted to enable identical protein binding activity. Involved in several processes, including positive regulation of brown fat cell differentiation; positive regulation of lipid storage; and positive regulation of white fat cell proliferation. Predicted to be located in extracellular region. 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=0.089321315).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001301009.2. 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
	VSTM2A	NM_001301009.2	MANE Select	c.634+3829G>C		intron	N/A	NP_001287938.1	F8W8J5
	VSTM2A	NM_182546.4		c.634+3829G>C		intron	N/A	NP_872352.2	Q8TAG5-1
	VSTM2A	NR_133927.2		n.444+3829G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VSTM2A	ENST00000402613.4	TSL:2 MANE Select	c.634+3829G>C		intron	N/A	ENSP00000384103.3	F8W8J5
	VSTM2A	ENST00000404951.5	TSL:5	c.767G>C	p.Arg256Pro	missense	Exon 5 of 6	ENSP00000384701.1	B5MCX6
	VSTM2A	ENST00000407838.7	TSL:3	c.634+3829G>C		intron	N/A	ENSP00000384967.3	Q8TAG5-1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151928 Hom.: 0 Cov.: 31

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 Cov.: 36

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151928 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74174

African (AFR) AF: 0.00 AC: 0 AN: 41318

American (AMR) AF: 0.00 AC: 0 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10560

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 1217

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.25
DANN	Benign	0.86
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0014	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-1.0	T
PhyloP100		-1.0
PROVEAN	Benign	0.060	N
REVEL	Benign	0.022
Sift	Uncertain	0.029	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.18	B
Vest4		0.099
MutPred		0.13		Gain of glycosylation at T253 (P = 0.0242)
MVP		0.16
ClinPred		0.075	T
GERP RS		0.32
Mutation Taster		=98/2	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: rs68106607; hg19: chr7-54621692;