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GeneBe

8-85442084-G-A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_005181.4(CA3):c.244G>A(p.Gly82Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000729 in 1,371,660 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

CA3
NM_005181.4 missense

Scores

8
4
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.35
Variant links:
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]
CA3-AS1 (HGNC:51657): (CA3 antisense RNA 1)

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.95

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CA3NM_005181.4 linkuse as main transcriptc.244G>A p.Gly82Ser missense_variant 3/7 ENST00000285381.3
CA3-AS1NR_121630.1 linkuse as main transcriptn.554C>T non_coding_transcript_exon_variant 3/3
CA3-AS1NR_121631.1 linkuse as main transcriptn.326C>T non_coding_transcript_exon_variant 3/3
CA3-AS1NR_121632.1 linkuse as main transcriptn.343C>T non_coding_transcript_exon_variant 3/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CA3ENST00000285381.3 linkuse as main transcriptc.244G>A p.Gly82Ser missense_variant 3/71 NM_005181.4 P1
CA3-AS1ENST00000521761.6 linkuse as main transcriptn.554C>T non_coding_transcript_exon_variant 3/34

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
7.29e-7
AC:
1
AN:
1371660
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
688060
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.71e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

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 submitterclinical testingAmbry GeneticsMar 21, 2023The c.244G>A (p.G82S) alteration is located in exon 3 (coding exon 3) of the CA3 gene. This alteration results from a G to A substitution at nucleotide position 244, causing the glycine (G) at amino acid position 82 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.77
BayesDel_addAF
Pathogenic
0.36
D
BayesDel_noAF
Pathogenic
0.28
Cadd
Pathogenic
27
Dann
Uncertain
1.0
Eigen
Pathogenic
1.1
Eigen_PC
Pathogenic
1.1
FATHMM_MKL
Pathogenic
1.0
D
M_CAP
Benign
0.033
D
MetaRNN
Pathogenic
0.95
D;D
MetaSVM
Uncertain
0.49
D
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.67
T
PROVEAN
Pathogenic
-6.0
D;D
REVEL
Uncertain
0.63
Polyphen
1.0
.;D
Vest4
0.96
MutPred
0.84
.;Gain of phosphorylation at G82 (P = 0.0208);
MVP
0.95
MPC
0.44
ClinPred
1.0
D
GERP RS
6.2
Varity_R
0.95
gMVP
0.91

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-86354313; API