NM_001218.5:c.956_957delTG
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_001218.5(CA12):c.956_957delTG(p.Val319GlyfsTer17) variant causes a frameshift change. The variant allele was found at a frequency of 0.0000545 in 1,614,116 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Consequence
NM_001218.5 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CA12 | ENST00000178638.8 | c.956_957delTG | p.Val319GlyfsTer17 | frameshift_variant | Exon 10 of 11 | 1 | NM_001218.5 | ENSP00000178638.3 | ||
CA12 | ENST00000344366.7 | c.923_924delTG | p.Val308GlyfsTer17 | frameshift_variant | Exon 9 of 10 | 1 | ENSP00000343088.3 | |||
CA12 | ENST00000422263.2 | c.743_744delTG | p.Val248GlyfsTer17 | frameshift_variant | Exon 8 of 9 | 2 | ENSP00000403028.2 | |||
CA12 | ENST00000560666.1 | n.166_167delTG | non_coding_transcript_exon_variant | Exon 2 of 3 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152194Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000302 AC: 76AN: 251404Hom.: 0 AF XY: 0.000206 AC XY: 28AN XY: 135878
GnomAD4 exome AF: 0.0000561 AC: 82AN: 1461804Hom.: 0 AF XY: 0.0000399 AC XY: 29AN XY: 727200
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152312Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74476
ClinVar
Submissions by phenotype
Isolated hyperchlorhidrosis Pathogenic:1
This variant deletes two nucleotides resulting in an amino acid alteration, replacing a valine (V) with a glycine (G) at codon 319 creating a premature stop signal in the new reading frame noted as p.V319Gfs*17. The substitution is predicted to result in a non-functional CA12 protein, either through protein truncation or nonsense-mediated mRNA decay. This mutation is considered a non-tolerated amino acid change based on in silico prediction algorithms (disease causing), it has not been reported in the ClinVar Database (NCBI National Library of Medicine, NIH), but it has been described in 27 alleles out of 120522, in the ExAC database, all of them belonging to heterozygous carries of Latino origin. Based on these findings and the limited literature regarding this substitution we consider it as a likely pathogenic variant. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at