rs1489283586

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

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

Scores

2
4
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.29
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
VSTM2BNM_001146339.2 linkc.59C>A p.Ala20Asp missense_variant Exon 1 of 5 ENST00000335523.8 NP_001139811.1 A6NLU5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
VSTM2BENST00000335523.8 linkc.59C>A p.Ala20Asp missense_variant Exon 1 of 5 5 NM_001146339.2 ENSP00000335038.6 A6NLU5
ENSG00000266248ENST00000579268.1 linkn.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
show subpopulations
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; API