11-87038175-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_022918.4(TMEM135):c.130C>T(p.Pro44Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
TMEM135
NM_022918.4 missense
NM_022918.4 missense
Scores
1
6
11
Clinical Significance
Conservation
PhyloP100: 5.40
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 Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.40756762).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMEM135 | NM_022918.4 | c.130C>T | p.Pro44Ser | missense_variant | 1/15 | ENST00000305494.6 | |
TMEM135 | NM_001168724.2 | c.130C>T | p.Pro44Ser | missense_variant | 1/14 | ||
TMEM135 | NR_033149.2 | n.242C>T | non_coding_transcript_exon_variant | 1/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMEM135 | ENST00000305494.6 | c.130C>T | p.Pro44Ser | missense_variant | 1/15 | 1 | NM_022918.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461870Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727238
GnomAD4 exome
AF:
AC:
3
AN:
1461870
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
727238
Gnomad4 AFR exome
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Gnomad4 EAS exome
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Gnomad4 SAS exome
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Gnomad4 FIN exome
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Gnomad4 NFE exome
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Gnomad4 OTH exome
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GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
Alfa
AF:
Hom.:
Bravo
AF:
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 | Oct 04, 2022 | The c.130C>T (p.P44S) alteration is located in exon 1 (coding exon 1) of the TMEM135 gene. This alteration results from a C to T substitution at nucleotide position 130, causing the proline (P) at amino acid position 44 to be replaced by a serine (S). 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
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Uncertain
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.;L
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T
Sift4G
Benign
T;T;D;T
Polyphen
B;.;.;P
Vest4
MutPred
Gain of MoRF binding (P = 0.0958);Gain of MoRF binding (P = 0.0958);Gain of MoRF binding (P = 0.0958);Gain of MoRF binding (P = 0.0958);
MVP
MPC
0.68
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at