NM_018426.3:c.724C>G

Variant names:

• chr6-44141040-C-G
• 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.33

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]

ACMG classification

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
TMEM63B	NM_018426.3	c.724C>G	p.Leu242Val	missense_variant	Exon 10 of 24	ENST00000323267.11	NP_060896.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM63B	ENST00000323267.11	c.724C>G	p.Leu242Val	missense_variant	Exon 10 of 24	5	NM_018426.3	ENSP00000327154.6

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

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;