rs775067652
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PP3_StrongPP5_Moderate
The NM_001218.5(CA12):c.363C>A(p.His121Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,936 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
CA12
NM_001218.5 missense
NM_001218.5 missense
Scores
14
4
1
Clinical Significance
Conservation
PhyloP100: 3.67
Genes affected
CA12 (HGNC:1371): (carbonic anhydrase 12) Carbonic anhydrases (CAs) are a large family of zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide. They participate in a variety of biological processes, including respiration, calcification, acid-base balance, bone resorption, and the formation of aqueous humor, cerebrospinal fluid, saliva, and gastric acid. This gene product is a type I membrane protein that is highly expressed in normal tissues, such as kidney, colon and pancreas, and has been found to be overexpressed in 10% of clear cell renal carcinomas. Three transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jun 2014]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PM1
?
In a binding_site (size 0) in uniprot entity CAH12_HUMAN
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.993
PP5
?
Variant 15-63345543-G-T is Pathogenic according to our data. Variant chr15-63345543-G-T is described in ClinVar as [Pathogenic]. Clinvar id is 218368.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CA12 | NM_001218.5 | c.363C>A | p.His121Gln | missense_variant | 4/11 | ENST00000178638.8 | |
CA12 | NM_206925.3 | c.363C>A | p.His121Gln | missense_variant | 4/10 | ||
CA12 | NM_001293642.2 | c.183C>A | p.His61Gln | missense_variant | 3/9 | ||
CA12 | NR_135511.2 | n.536C>A | non_coding_transcript_exon_variant | 4/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CA12 | ENST00000178638.8 | c.363C>A | p.His121Gln | missense_variant | 4/11 | 1 | NM_001218.5 | A1 | |
CA12 | ENST00000344366.7 | c.363C>A | p.His121Gln | missense_variant | 4/10 | 1 | P4 | ||
CA12 | ENST00000422263.2 | c.183C>A | p.His61Gln | missense_variant | 3/9 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000400 AC: 1AN: 250306Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135374
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1460936Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 726788
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GnomAD4 genome ? Cov.: 32
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32
ExAC
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Isolated hyperchlorhidrosis Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | Aug 27, 2018 | - - |
Pathogenic, criteria provided, single submitter | research | Garry R Cutting Laboratory, Johns Hopkins University | Oct 20, 2015 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Pathogenic
D;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
H;H;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D;D
Sift4G
Pathogenic
D;D;D
Polyphen
D;D;D
Vest4
MutPred
Gain of disorder (P = 0.2047);Gain of disorder (P = 0.2047);.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at