rs1489283586

Variant names:

• chr19-29526642-C-A
• NM_001146339.2:c.59C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-29526642-C-A
• chr19-29526642-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001146339.2(VSTM2B):​c.59C>A​(p.Ala20Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000145 in 1,377,912 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A20V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: VSTM2B NM_001146339.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.29

Genes affected

VSTM2B (HGNC:33595): (V-set and transmembrane domain containing 2B) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000266248 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3944212).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VSTM2B	NM_001146339.2	c.59C>A	p.Ala20Asp	missense_variant	Exon 1 of 5	ENST00000335523.8	NP_001139811.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VSTM2B	ENST00000335523.8	c.59C>A	p.Ala20Asp	missense_variant	Exon 1 of 5	5	NM_001146339.2	ENSP00000335038.6
ENSG00000266248	ENST00000579268.1	n.307G>T		non_coding_transcript_exon_variant	Exon 1 of 2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000145 AC: 2 AN: 1377912 Hom.: 0 Cov.: 31 AF XY: 0.00000294 AC XY: 2 AN XY: 680082

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000256

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Benign	-0.043	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.031	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.46	T
M_CAP	Pathogenic	0.31	D
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.20
Sift	Uncertain	0.017	D
Sift4G	Benign	0.072	T
Polyphen		0.084	B
Vest4		0.69
MutPred		0.53		Loss of glycosylation at P15 (P = 0.1207);
MVP		0.095
ClinPred		0.57	D
GERP RS		2.8
Varity_R		0.27
gMVP		0.75

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-30017549;