chr11-87302352-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_022918.4(TMEM135):c.608A>G(p.Tyr203Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,461,630 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y203H) has been classified as Benign.
Frequency
Consequence
NM_022918.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMEM135 | NM_022918.4 | c.608A>G | p.Tyr203Cys | missense_variant | 8/15 | ENST00000305494.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMEM135 | ENST00000305494.6 | c.608A>G | p.Tyr203Cys | missense_variant | 8/15 | 1 | NM_022918.4 | P1 | |
TMEM135 | ENST00000340353.11 | c.542A>G | p.Tyr181Cys | missense_variant | 7/14 | 1 | |||
TMEM135 | ENST00000532959.5 | c.221A>G | p.Tyr74Cys | missense_variant | 5/12 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251282Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135806
GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461630Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7AN XY: 727116
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 22, 2024 | The c.608A>G (p.Y203C) alteration is located in exon 8 (coding exon 8) of the TMEM135 gene. This alteration results from a A to G substitution at nucleotide position 608, causing the tyrosine (Y) at amino acid position 203 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at