rs397517836
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_138691.3(TMC1):āc.1369T>Cā(p.Phe457Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,814 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ). Synonymous variant affecting the same amino acid position (i.e. F457F) has been classified as Likely benign.
Frequency
Consequence
NM_138691.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMC1 | NM_138691.3 | c.1369T>C | p.Phe457Leu | missense_variant | 16/24 | ENST00000297784.10 | |
TMC1 | XM_017014256.2 | c.1372T>C | p.Phe458Leu | missense_variant | 13/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMC1 | ENST00000297784.10 | c.1369T>C | p.Phe457Leu | missense_variant | 16/24 | 1 | NM_138691.3 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251242Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135772
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461814Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727208
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 01, 2011 | Variant classified as Uncertain Significance - Favor Benign. The Phe457Leu varia nt in TMC1 has not been reported in the literature nor previously identified by our laboratory. Computational analyses (PolyPhen2, SIFT, AlignGVGD) provide inco nsistent predictions on the pathogenicity of this variant. In summary, the clini cal significance of this variant cannot be determined with certainty at this tim e. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at