rs765966901
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001127198.5(TMC6):āc.73T>Cā(p.Tyr25His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,613,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y25C) has been classified as Uncertain significance.
Frequency
Consequence
NM_001127198.5 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 |
---|---|---|---|---|---|---|---|
TMC6 | NM_001127198.5 | c.73T>C | p.Tyr25His | missense_variant | 3/20 | ENST00000590602.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMC6 | ENST00000590602.6 | c.73T>C | p.Tyr25His | missense_variant | 3/20 | 2 | NM_001127198.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000986 AC: 15AN: 152080Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000240 AC: 6AN: 249776Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135542
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461140Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 726844
GnomAD4 genome AF: 0.0000986 AC: 15AN: 152080Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9AN XY: 74276
ClinVar
Submissions by phenotype
Epidermodysplasia verruciformis, susceptibility to, 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago | Mar 30, 2021 | TMC6 NM_007267.7 exon 3 p.Tyr25His (c.73T>C): This variant has not been reported in the literature but is present in 0.03% (8/24734) of African alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/17-76122713-A-G?dataset=gnomad_r2_1). This variant is present in ClinVar (Variation ID:565521). Evolutionary conservation suggests that this variant may not impact the protein; computational predictive tools for this variant are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. - |
Epidermodysplasia verruciformis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 27, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at