19-29530051-C-A

Variant names:

• chr19-29530051-C-A
• NM_001146339.2:c.530C>A

Variant summary

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

The NM_001146339.2(VSTM2B):​c.530C>A​(p.Ala177Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: VSTM2B NM_001146339.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.44
• Publications: 0 publications found

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]

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=0.24023646).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001146339.2. 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
	VSTM2B	NM_001146339.2	MANE Select	c.530C>A	p.Ala177Asp	missense	Exon 4 of 5	NP_001139811.1	A6NLU5
	VSTM2B	NM_001384640.1		c.500C>A	p.Ala167Asp	missense	Exon 3 of 4	NP_001371569.1
	VSTM2B	NM_001384641.1		c.392C>A	p.Ala131Asp	missense	Exon 4 of 5	NP_001371570.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VSTM2B	ENST00000335523.8	TSL:5 MANE Select	c.530C>A	p.Ala177Asp	missense	Exon 4 of 5	ENSP00000335038.6	A6NLU5
	VSTM2B	ENST00000915703.1		c.602C>A	p.Ala201Asp	missense	Exon 6 of 7	ENSP00000585762.1
	VSTM2B	ENST00000952478.1		c.596C>A	p.Ala199Asp	missense	Exon 5 of 6	ENSP00000622537.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1365074 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 673194

African (AFR) AF: 0.00 AC: 0 AN: 28736

American (AMR) AF: 0.00 AC: 0 AN: 33784

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24350

East Asian (EAS) AF: 0.00 AC: 0 AN: 33402

South Asian (SAS) AF: 0.00 AC: 0 AN: 76840

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34680

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5000

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1071296

Other (OTH) AF: 0.00 AC: 0 AN: 56986

GnomAD4 genome Cov.: 33

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	0.14
BayesDel_addAF	Uncertain	0.021	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	17
DANN	Uncertain	0.97
DEOGEN2	Benign	0.0077	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.60	T
M_CAP	Pathogenic	0.70	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		1.4
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-2.0	N
REVEL	Uncertain	0.31
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.12	T
Polyphen		0.037	B
Vest4		0.23
MutPred		0.10		Loss of helix (P = 0.0167)
MVP		0.16
ClinPred		0.65	D
GERP RS		3.8
Varity_R		0.44
gMVP		0.51
Mutation Taster		=77/23	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

hg19: chr19-30020958;