12-47966717-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001143842.2(TMEM106C):c.587C>T(p.Pro196Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000384 in 1,613,958 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001143842.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TMEM106C | ENST00000429772.7 | c.587C>T | p.Pro196Leu | missense_variant | Exon 6 of 8 | 2 | NM_001143842.2 | ENSP00000400471.2 | ||
TMEM106C | ENST00000552546.5 | c.374C>T | p.Pro125Leu | missense_variant | Exon 5 of 7 | 4 | ENSP00000448268.1 | |||
TMEM106C | ENST00000548640.5 | c.317C>T | p.Pro106Leu | missense_variant | Exon 5 of 7 | 3 | ENSP00000447254.1 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152108Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000994 AC: 25AN: 251488Hom.: 0 AF XY: 0.000132 AC XY: 18AN XY: 135918
GnomAD4 exome AF: 0.0000376 AC: 55AN: 1461850Hom.: 0 Cov.: 31 AF XY: 0.0000619 AC XY: 45AN XY: 727228
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152108Hom.: 0 Cov.: 33 AF XY: 0.0000808 AC XY: 6AN XY: 74302
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.587C>T (p.P196L) alteration is located in exon 6 (coding exon 5) of the TMEM106C gene. This alteration results from a C to T substitution at nucleotide position 587, causing the proline (P) at amino acid position 196 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