chr12-43844784-A-G
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_032256.3(TMEM117):āc.133A>Gā(p.Ile45Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000752 in 1,461,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0000075 ( 0 hom. )
Consequence
TMEM117
NM_032256.3 missense
NM_032256.3 missense
Scores
3
14
Clinical Significance
Conservation
PhyloP100: 5.22
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=0.0680494).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMEM117 | NM_032256.3 | c.133A>G | p.Ile45Val | missense_variant | 2/8 | ENST00000266534.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMEM117 | ENST00000266534.8 | c.133A>G | p.Ile45Val | missense_variant | 2/8 | 1 | NM_032256.3 | P1 | |
TMEM117 | ENST00000551577.5 | c.133A>G | p.Ile45Val | missense_variant | 2/7 | 1 | |||
TMEM117 | ENST00000546868.5 | c.133A>G | p.Ile45Val | missense_variant, NMD_transcript_variant | 2/7 | 1 | |||
TMEM117 | ENST00000546387.1 | n.391A>G | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
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32
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251454Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135906
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GnomAD4 exome AF: 0.00000752 AC: 11AN: 1461822Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6AN XY: 727212
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GnomAD4 genome Cov.: 32
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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 | Mar 11, 2024 | The c.133A>G (p.I45V) alteration is located in exon 2 (coding exon 1) of the TMEM117 gene. This alteration results from a A to G substitution at nucleotide position 133, causing the isoleucine (I) at amino acid position 45 to be replaced by a valine (V). 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
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MutPred
Gain of catalytic residue at N49 (P = 0.001);Gain of catalytic residue at N49 (P = 0.001);
MVP
MPC
0.95
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