NM_018426.3:c.724C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018426.3(TMEM63B):​c.724C>G​(p.Leu242Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

TMEM63B
NM_018426.3 missense

Scores

2
10
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.33
Variant links:
Genes affected
TMEM63B (HGNC:17735): (transmembrane protein 63B) Predicted to enable calcium activated cation channel activity; mechanosensitive ion channel activity; and osmolarity-sensing cation channel activity. Predicted to be involved in cation transmembrane transport. Located in actin cytoskeleton and plasma 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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TMEM63BNM_018426.3 linkc.724C>G p.Leu242Val missense_variant Exon 10 of 24 ENST00000323267.11 NP_060896.1 Q5T3F8-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TMEM63BENST00000323267.11 linkc.724C>G p.Leu242Val missense_variant Exon 10 of 24 5 NM_018426.3 ENSP00000327154.6 Q5T3F8-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Dec 21, 2023
GeneDx
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.54
BayesDel_addAF
Benign
-0.035
T
BayesDel_noAF
Benign
-0.29
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.21
T;T
Eigen
Uncertain
0.53
Eigen_PC
Uncertain
0.47
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.94
.;D
M_CAP
Benign
0.034
D
MetaRNN
Uncertain
0.59
D;D
MetaSVM
Benign
-0.72
T
MutationAssessor
Uncertain
2.3
M;M
PrimateAI
Pathogenic
0.84
D
PROVEAN
Uncertain
-2.9
D;D
REVEL
Uncertain
0.33
Sift
Uncertain
0.011
D;D
Sift4G
Benign
0.063
T;T
Polyphen
1.0
D;D
Vest4
0.63
MutPred
0.69
Loss of stability (P = 0.0489);Loss of stability (P = 0.0489);
MVP
0.22
MPC
1.6
ClinPred
0.98
D
GERP RS
4.3
Varity_R
0.45
gMVP
0.85

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: chr6-44108777; API