16-19440706-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001261841.2(TMC5):c.668C>T(p.Pro223Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,614,048 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001261841.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TMC5 | NM_001261841.2 | c.668C>T | p.Pro223Leu | missense_variant | Exon 3 of 22 | ENST00000542583.7 | NP_001248770.1 | |
TMC5 | NM_001105248.1 | c.668C>T | p.Pro223Leu | missense_variant | Exon 3 of 22 | NP_001098718.1 | ||
TMC5 | NM_001308161.1 | c.668C>T | p.Pro223Leu | missense_variant | Exon 3 of 21 | NP_001295090.1 | ||
TMC5 | NM_001105249.1 | c.668C>T | p.Pro223Leu | missense_variant | Exon 3 of 21 | NP_001098719.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TMC5 | ENST00000542583.7 | c.668C>T | p.Pro223Leu | missense_variant | Exon 3 of 22 | 2 | NM_001261841.2 | ENSP00000446274.2 | ||
TMC5 | ENST00000381414.8 | c.668C>T | p.Pro223Leu | missense_variant | Exon 3 of 21 | 1 | ENSP00000370822.4 | |||
TMC5 | ENST00000396229.6 | c.668C>T | p.Pro223Leu | missense_variant | Exon 3 of 22 | 5 | ENSP00000379531.2 | |||
TMC5 | ENST00000541464.5 | c.668C>T | p.Pro223Leu | missense_variant | Exon 3 of 21 | 2 | ENSP00000441227.1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152158Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000322 AC: 8AN: 248468Hom.: 0 AF XY: 0.0000370 AC XY: 5AN XY: 134978
GnomAD4 exome AF: 0.0000157 AC: 23AN: 1461890Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 10AN XY: 727246
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152158Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74332
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.668C>T (p.P223L) alteration is located in exon 3 (coding exon 1) of the TMC5 gene. This alteration results from a C to T substitution at nucleotide position 668, causing the proline (P) at amino acid position 223 to be replaced by a leucine (L). 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