12-128415308-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001136103.3(TMEM132C):c.662C>T(p.Pro221Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000673 in 1,593,602 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001136103.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TMEM132C | NM_001136103.3 | c.662C>T | p.Pro221Leu | missense_variant | 2/9 | ENST00000435159.3 | NP_001129575.2 | |
TMEM132C | NM_001387058.1 | c.602C>T | p.Pro201Leu | missense_variant | 2/9 | NP_001373987.1 | ||
TMEM132C | XM_047429886.1 | c.662C>T | p.Pro221Leu | missense_variant | 2/9 | XP_047285842.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TMEM132C | ENST00000435159.3 | c.662C>T | p.Pro221Leu | missense_variant | 2/9 | 5 | NM_001136103.3 | ENSP00000410852 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000572 AC: 87AN: 152052Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000432 AC: 92AN: 213112Hom.: 0 AF XY: 0.000364 AC XY: 42AN XY: 115328
GnomAD4 exome AF: 0.000683 AC: 985AN: 1441434Hom.: 0 Cov.: 36 AF XY: 0.000656 AC XY: 469AN XY: 715064
GnomAD4 genome AF: 0.000572 AC: 87AN: 152168Hom.: 1 Cov.: 32 AF XY: 0.000578 AC XY: 43AN XY: 74374
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 06, 2021 | The c.662C>T (p.P221L) alteration is located in exon 2 (coding exon 2) of the TMEM132C gene. This alteration results from a C to T substitution at nucleotide position 662, causing the proline (P) at amino acid position 221 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