NM_024847.4:c.41C>T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_024847.4(TMC7):c.41C>T(p.Pro14Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000386 in 1,503,202 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. P14S) has been classified as Uncertain significance.
Frequency
Consequence
NM_024847.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TMC7 | ENST00000304381.10 | c.41C>T | p.Pro14Leu | missense_variant | Exon 1 of 16 | 1 | NM_024847.4 | ENSP00000304710.5 | ||
TMC7 | ENST00000569532.5 | c.41C>T | p.Pro14Leu | missense_variant | Exon 1 of 15 | 2 | ENSP00000455041.1 | |||
TMC7 | ENST00000568469.5 | n.82C>T | non_coding_transcript_exon_variant | Exon 1 of 10 | 2 | |||||
TMC7 | ENST00000421369.3 | c.-741C>T | upstream_gene_variant | 1 | ENSP00000397081.3 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152158Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000299 AC: 3AN: 100194Hom.: 0 AF XY: 0.0000179 AC XY: 1AN XY: 55954
GnomAD4 exome AF: 0.0000407 AC: 55AN: 1351044Hom.: 0 Cov.: 30 AF XY: 0.0000420 AC XY: 28AN XY: 666346
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152158Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74332
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.41C>T (p.P14L) alteration is located in exon 1 (coding exon 1) of the TMC7 gene. This alteration results from a C to T substitution at nucleotide position 41, causing the proline (P) at amino acid position 14 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