6-44146858-C-T

Variant summary

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

The NM_018426.3(TMEM63B):​c.794C>T​(p.Pro265Leu) variant causes a missense change. 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: 32)

Consequence

TMEM63B
NM_018426.3 missense

Scores

2
8
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.86
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]

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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=0.3720423).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TMEM63BNM_018426.3 linkc.794C>T p.Pro265Leu missense_variant Exon 11 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.794C>T p.Pro265Leu missense_variant Exon 11 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

Inborn genetic diseases Uncertain:1
Jun 07, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.794C>T (p.P265L) alteration is located in exon 11 (coding exon 10) of the TMEM63B gene. This alteration results from a C to T substitution at nucleotide position 794, causing the proline (P) at amino acid position 265 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.23
BayesDel_addAF
Benign
-0.075
T
BayesDel_noAF
Benign
-0.35
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.33
T;T
Eigen
Uncertain
0.45
Eigen_PC
Uncertain
0.48
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.97
.;D
M_CAP
Benign
0.022
T
MetaRNN
Benign
0.37
T;T
MetaSVM
Benign
-0.89
T
MutationAssessor
Uncertain
2.5
M;M
PrimateAI
Uncertain
0.64
T
PROVEAN
Pathogenic
-8.6
D;D
REVEL
Benign
0.26
Sift
Uncertain
0.0010
D;D
Sift4G
Uncertain
0.0020
D;D
Polyphen
0.70
P;P
Vest4
0.35
MutPred
0.67
Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);
MVP
0.17
MPC
1.2
ClinPred
0.99
D
GERP RS
4.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.43
gMVP
0.79

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: chr6-44114595; API