chr15-63340371-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001218.5(CA12):c.664C>T(p.Arg222Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,613,948 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000011 ( 0 hom. )
Consequence
CA12
NM_001218.5 missense
NM_001218.5 missense
Scores
7
12
Clinical Significance
Conservation
PhyloP100: -0.0480
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 Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CA12 | NM_001218.5 | c.664C>T | p.Arg222Trp | missense_variant | 7/11 | ENST00000178638.8 | NP_001209.1 | |
LOC124903506 | XR_007064676.1 | n.768-1443G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CA12 | ENST00000178638.8 | c.664C>T | p.Arg222Trp | missense_variant | 7/11 | 1 | NM_001218.5 | ENSP00000178638 | A1 | |
CA12 | ENST00000344366.7 | c.664C>T | p.Arg222Trp | missense_variant | 7/10 | 1 | ENSP00000343088 | P4 | ||
CA12 | ENST00000422263.2 | c.484C>T | p.Arg162Trp | missense_variant | 6/9 | 2 | ENSP00000403028 | |||
CA12 | ENST00000558287.1 | n.212C>T | non_coding_transcript_exon_variant | 3/3 | 3 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152114Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000278 AC: 7AN: 251454Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135898
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GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461834Hom.: 0 Cov.: 31 AF XY: 0.0000165 AC XY: 12AN XY: 727222
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152114Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74300
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 12, 2021 | The c.664C>T (p.R222W) alteration is located in exon 7 (coding exon 7) of the CA12 gene. This alteration results from a C to T substitution at nucleotide position 664, causing the arginine (R) at amino acid position 222 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
D;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
M;M;.
MutationTaster
Benign
N;N;N
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D;D
REVEL
Benign
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
D;D;D
Vest4
MutPred
Loss of methylation at R222 (P = 0.0214);Loss of methylation at R222 (P = 0.0214);.;
MVP
MPC
ClinPred
D
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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