12-43944315-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_032256.3(TMEM117):c.383C>T(p.Thr128Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000267 in 1,612,212 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000027 ( 0 hom. )
Consequence
TMEM117
NM_032256.3 missense
NM_032256.3 missense
Scores
17
Clinical Significance
Conservation
PhyloP100: 3.62
Genes affected
TMEM117 (HGNC:25308): (transmembrane protein 117) Involved in intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress. Located in endoplasmic reticulum 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 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.10465124).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMEM117 | NM_032256.3 | c.383C>T | p.Thr128Met | missense_variant | 3/8 | ENST00000266534.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMEM117 | ENST00000266534.8 | c.383C>T | p.Thr128Met | missense_variant | 3/8 | 1 | NM_032256.3 | P1 | |
TMEM117 | ENST00000551577.5 | c.383C>T | p.Thr128Met | missense_variant | 3/7 | 1 | |||
TMEM117 | ENST00000546868.5 | c.383C>T | p.Thr128Met | missense_variant, NMD_transcript_variant | 3/7 | 1 | |||
TMEM117 | ENST00000550495.1 | c.-23+99387C>T | intron_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152150Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000359 AC: 9AN: 250836Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135542
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GnomAD4 exome AF: 0.0000274 AC: 40AN: 1460062Hom.: 0 Cov.: 29 AF XY: 0.0000289 AC XY: 21AN XY: 726462
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152150Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74340
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 17, 2021 | The c.383C>T (p.T128M) alteration is located in exon 3 (coding exon 2) of the TMEM117 gene. This alteration results from a C to T substitution at nucleotide position 383, causing the threonine (T) at amino acid position 128 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MVP
MPC
0.37
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at