chr12-44388580-T-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_032256.3(TMEM117):c.1453T>G(p.Ser485Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000547 in 1,461,312 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 (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000055 ( 0 hom. )
Consequence
TMEM117
NM_032256.3 missense
NM_032256.3 missense
Scores
1
3
15
Clinical Significance
Conservation
PhyloP100: 3.69
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 Likely_benign. Variant got -2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.046407938).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMEM117 | NM_032256.3 | c.1453T>G | p.Ser485Ala | missense_variant | 8/8 | ENST00000266534.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMEM117 | ENST00000266534.8 | c.1453T>G | p.Ser485Ala | missense_variant | 8/8 | 1 | NM_032256.3 | P1 | |
TMEM117 | ENST00000551577.5 | c.*516T>G | 3_prime_UTR_variant | 7/7 | 1 | ||||
TMEM117 | ENST00000546868.5 | c.*930T>G | 3_prime_UTR_variant, NMD_transcript_variant | 7/7 | 1 | ||||
TMEM117 | ENST00000546978.1 | n.762T>G | non_coding_transcript_exon_variant | 3/3 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.0000240 AC: 6AN: 250294Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135206
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GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461312Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726968
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
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?
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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 | Sep 01, 2021 | The c.1453T>G (p.S485A) alteration is located in exon 8 (coding exon 7) of the TMEM117 gene. This alteration results from a T to G substitution at nucleotide position 1453, causing the serine (S) at amino acid position 485 to be replaced by an alanine (A). 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
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
D;N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Pathogenic
D
Polyphen
B
Vest4
MutPred
Gain of helix (P = 0.0225);
MVP
MPC
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