8-85439862-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005181.4(CA3):ā€‹c.185A>Gā€‹(p.Asn62Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000266 in 1,613,936 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000020 ( 0 hom., cov: 33)
Exomes š‘“: 0.000027 ( 0 hom. )

Consequence

CA3
NM_005181.4 missense

Scores

9
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.52
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]

Genome browser will be placed here

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
CA3NM_005181.4 linkuse as main transcriptc.185A>G p.Asn62Ser missense_variant 2/7 ENST00000285381.3 NP_005172.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CA3ENST00000285381.3 linkuse as main transcriptc.185A>G p.Asn62Ser missense_variant 2/71 NM_005181.4 ENSP00000285381 P1
CA3ENST00000520921.1 linkuse as main transcriptc.-47A>G 5_prime_UTR_variant 3/44 ENSP00000429760
CA3ENST00000522207.1 linkuse as main transcriptn.237A>G non_coding_transcript_exon_variant 2/32

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152180
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000318
AC:
8
AN:
251306
Hom.:
0
AF XY:
0.0000515
AC XY:
7
AN XY:
135842
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000528
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000274
AC:
40
AN:
1461638
Hom.:
0
Cov.:
32
AF XY:
0.0000358
AC XY:
26
AN XY:
727136
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000315
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152298
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74474
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000774
Hom.:
0
Bravo
AF:
0.0000491
ExAC
AF:
0.0000494
AC:
6
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000119

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 GeneticsJan 03, 2022The c.185A>G (p.N62S) alteration is located in exon 2 (coding exon 2) of the CA3 gene. This alteration results from a A to G substitution at nucleotide position 185, causing the asparagine (N) at amino acid position 62 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
Benign
0.16
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.45
CADD
Benign
20
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.55
D
Eigen
Uncertain
0.54
Eigen_PC
Uncertain
0.52
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.88
D
M_CAP
Benign
0.023
T
MetaRNN
Uncertain
0.51
D
MetaSVM
Benign
-0.70
T
MutationAssessor
Benign
1.9
L
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.60
T
PROVEAN
Uncertain
-2.9
D
REVEL
Benign
0.27
Sift
Benign
0.15
T
Sift4G
Benign
0.36
T
Polyphen
1.0
D
Vest4
0.23
MVP
0.77
MPC
0.59
ClinPred
0.52
D
GERP RS
5.8
Varity_R
0.49
gMVP
0.85

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs542149751; hg19: chr8-86352091; API