8-85438937-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_005181.4(CA3):c.28C>T(p.His10Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000845 in 1,551,144 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
Genomes: 𝑓 0.00018 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000074 ( 0 hom. )
Consequence
CA3
NM_005181.4 missense
NM_005181.4 missense
Scores
9
10
Clinical Significance
Conservation
PhyloP100: 3.18
Genes affected
CA3 (HGNC:1374): (carbonic anhydrase 3) Carbonic anhydrase III (CAIII) is a member of a multigene family (at least six separate genes are known) that encodes carbonic anhydrase isozymes. These carbonic anhydrases are a class of metalloenzymes that catalyze the reversible hydration of carbon dioxide and are differentially expressed in a number of cell types. The expression of the CA3 gene is strictly tissue specific and present at high levels in skeletal muscle and much lower levels in cardiac and smooth muscle. A proportion of carriers of Duchenne muscle dystrophy have a higher CA3 level than normal. The gene spans 10.3 kb and contains seven exons and six introns. [provided by RefSeq, Oct 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.11455858).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CA3 | NM_005181.4 | c.28C>T | p.His10Tyr | missense_variant | 1/7 | ENST00000285381.3 | NP_005172.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CA3 | ENST00000285381.3 | c.28C>T | p.His10Tyr | missense_variant | 1/7 | 1 | NM_005181.4 | ENSP00000285381 | P1 | |
CA3 | ENST00000520921.1 | c.-197-775C>T | intron_variant | 4 | ENSP00000429760 | |||||
CA3 | ENST00000522207.1 | n.80C>T | non_coding_transcript_exon_variant | 1/3 | 2 |
Frequencies
GnomAD3 genomes AF: 0.000177 AC: 27AN: 152254Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000142 AC: 22AN: 154808Hom.: 0 AF XY: 0.000147 AC XY: 12AN XY: 81692
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GnomAD4 exome AF: 0.0000743 AC: 104AN: 1398890Hom.: 0 Cov.: 31 AF XY: 0.0000768 AC XY: 53AN XY: 689982
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GnomAD4 genome AF: 0.000177 AC: 27AN: 152254Hom.: 0 Cov.: 33 AF XY: 0.000255 AC XY: 19AN XY: 74378
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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 | Dec 27, 2022 | The c.28C>T (p.H10Y) alteration is located in exon 1 (coding exon 1) of the CA3 gene. This alteration results from a C to T substitution at nucleotide position 28, causing the histidine (H) at amino acid position 10 to be replaced by a tyrosine (Y). 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
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
N
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Uncertain
D
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Gain of catalytic residue at H10 (P = 0.0121);
MVP
MPC
ClinPred
T
GERP RS
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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