chr17-78131671-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_152468.5(TMC8):āc.83G>Cā(p.Arg28Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000891 in 1,570,558 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Synonymous variant affecting the same amino acid position (i.e. R28R) has been classified as Likely benign.
Frequency
Consequence
NM_152468.5 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 |
---|---|---|---|---|---|---|---|
TMC8 | NM_152468.5 | c.83G>C | p.Arg28Pro | missense_variant | 2/16 | ENST00000318430.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMC8 | ENST00000318430.10 | c.83G>C | p.Arg28Pro | missense_variant | 2/16 | 1 | NM_152468.5 | P2 | |
TMC6 | ENST00000322914.7 | c.-75+670C>G | intron_variant | 1 | P1 | ||||
TMC8 | ENST00000589691.1 | c.-372+266G>C | intron_variant | 1 | A2 | ||||
TMC8 | ENST00000590799.5 | n.465G>C | non_coding_transcript_exon_variant | 2/4 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152252Hom.: 1 Cov.: 34
GnomAD3 exomes AF: 0.0000289 AC: 5AN: 172850Hom.: 0 AF XY: 0.0000213 AC XY: 2AN XY: 93788
GnomAD4 exome AF: 0.00000776 AC: 11AN: 1418188Hom.: 0 Cov.: 32 AF XY: 0.00000855 AC XY: 6AN XY: 701598
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152370Hom.: 1 Cov.: 34 AF XY: 0.0000134 AC XY: 1AN XY: 74514
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 26, 2023 | The c.83G>C (p.R28P) alteration is located in exon 2 (coding exon 1) of the TMC8 gene. This alteration results from a G to C substitution at nucleotide position 83, causing the arginine (R) at amino acid position 28 to be replaced by a proline (P). 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