chr11-87318221-A-G
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_022918.4(TMEM135):c.1162A>G(p.Ile388Val) variant causes a missense change. The variant allele was found at a frequency of 0.000241 in 1,611,520 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 Likely benign (★).
Frequency
Genomes: 𝑓 0.0012 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00014 ( 0 hom. )
Consequence
TMEM135
NM_022918.4 missense
NM_022918.4 missense
Scores
1
2
14
Clinical Significance
Conservation
PhyloP100: 7.09
Genes affected
TMEM135 (HGNC:26167): (transmembrane protein 135) Predicted to be involved in peroxisome organization. Predicted to act upstream of or within response to cold and response to food. Predicted to be located in mitochondrion and peroxisome. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.010766566).
BP6
?
Variant 11-87318221-A-G is Benign according to our data. Variant chr11-87318221-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3049524.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMEM135 | NM_022918.4 | c.1162A>G | p.Ile388Val | missense_variant | 13/15 | ENST00000305494.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMEM135 | ENST00000305494.6 | c.1162A>G | p.Ile388Val | missense_variant | 13/15 | 1 | NM_022918.4 | P1 | |
TMEM135 | ENST00000340353.11 | c.1096A>G | p.Ile366Val | missense_variant | 12/14 | 1 | |||
TMEM135 | ENST00000531643.1 | n.87A>G | non_coding_transcript_exon_variant | 1/3 | 1 | ||||
TMEM135 | ENST00000532959.5 | c.775A>G | p.Ile259Val | missense_variant | 10/12 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00123 AC: 187AN: 152124Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000353 AC: 88AN: 249248Hom.: 0 AF XY: 0.000252 AC XY: 34AN XY: 134768
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GnomAD4 exome AF: 0.000139 AC: 203AN: 1459278Hom.: 0 Cov.: 30 AF XY: 0.000106 AC XY: 77AN XY: 726076
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GnomAD4 genome ? AF: 0.00122 AC: 186AN: 152242Hom.: 0 Cov.: 32 AF XY: 0.00130 AC XY: 97AN XY: 74436
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
TMEM135-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 16, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
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
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
B;.;B
Vest4
MVP
MPC
0.31
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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