17-7436476-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_178518.3(TMEM102):​c.497C>T​(p.Pro166Leu) 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

TMEM102
NM_178518.3 missense

Scores

4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.93
Variant links:
Genes affected
TMEM102 (HGNC:26722): (transmembrane protein 102) Involved in regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway; response to cytokine; and signal transduction. Acts upstream of or within positive regulation of T cell migration and positive regulation of cell adhesion. Located in cell surface. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.17689684).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TMEM102NM_178518.3 linkc.497C>T p.Pro166Leu missense_variant Exon 3 of 3 ENST00000323206.2 NP_848613.1 Q8N9M5
TMEM102NM_001320444.1 linkc.497C>T p.Pro166Leu missense_variant Exon 2 of 2 NP_001307373.1 Q8N9M5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TMEM102ENST00000323206.2 linkc.497C>T p.Pro166Leu missense_variant Exon 3 of 3 1 NM_178518.3 ENSP00000315387.1 Q8N9M5
ENSG00000286007ENST00000651314.1 linkn.*385C>T downstream_gene_variant ENSP00000498964.1 A0A494C1D0

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jul 25, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.497C>T (p.P166L) alteration is located in exon 3 (coding exon 2) of the TMEM102 gene. This alteration results from a C to T substitution at nucleotide position 497, causing the proline (P) at amino acid position 166 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
0.11
BayesDel_addAF
Benign
-0.047
T
BayesDel_noAF
Benign
-0.31
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.011
T;T
Eigen
Benign
0.049
Eigen_PC
Benign
0.10
FATHMM_MKL
Benign
0.51
D
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.18
T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Uncertain
2.0
M;M
PrimateAI
Benign
0.39
T
PROVEAN
Benign
-1.6
N;N
REVEL
Benign
0.087
Sift
Uncertain
0.0020
D;D
Sift4G
Uncertain
0.0080
D;D
Polyphen
0.51
P;P
Vest4
0.35
MutPred
0.49
Loss of disorder (P = 0.0143);Loss of disorder (P = 0.0143);
MVP
0.63
ClinPred
0.94
D
GERP RS
4.4
Varity_R
0.14
gMVP
0.24

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: chr17-7339795; API