X-15764682-C-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_007220.4(CA5B):​c.247C>G​(p.Leu83Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000117 in 1,196,499 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L83R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000092 ( 0 hom., 1 hem., cov: 21)
Exomes 𝑓: 0.000012 ( 0 hom. 2 hem. )

Consequence

CA5B
NM_007220.4 missense

Scores

7
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.34
Variant links:
Genes affected
CA5B (HGNC:1378): (carbonic anhydrase 5B) 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. They show extensive diversity in tissue distribution and in their subcellular localization. This gene encodes carbonic anhydrase 5B. CA5B, and the related CA5A gene, has its expression localized in the mitochondria though CA5B has a wider tissue distribution than CA5A, which is restricted to the liver, kidneys, and skeletal muscle. A carbonic anhydrase pseudogene (CA5BP1) is adjacent to the CA5B gene and these two loci produce CA5BP1-CA5B readthrough transcripts. [provided by RefSeq, Jan 2019]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CA5BNM_007220.4 linkc.247C>G p.Leu83Val missense_variant Exon 3 of 8 ENST00000318636.8 NP_009151.1 Q9Y2D0A0A024RBW9
CA5BP1-CA5BNR_160544.1 linkn.1011C>G non_coding_transcript_exon_variant Exon 6 of 12
CA5BP1-CA5BNR_160545.1 linkn.1011C>G non_coding_transcript_exon_variant Exon 6 of 6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CA5BENST00000318636.8 linkc.247C>G p.Leu83Val missense_variant Exon 3 of 8 1 NM_007220.4 ENSP00000314099.3 Q9Y2D0

Frequencies

GnomAD3 genomes
AF:
0.00000916
AC:
1
AN:
109221
Hom.:
0
Cov.:
21
AF XY:
0.0000318
AC XY:
1
AN XY:
31473
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:
0.0000190
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000120
AC:
13
AN:
1087278
Hom.:
0
Cov.:
28
AF XY:
0.00000565
AC XY:
2
AN XY:
353764
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:
0.0000156
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000916
AC:
1
AN:
109221
Hom.:
0
Cov.:
21
AF XY:
0.0000318
AC XY:
1
AN XY:
31473
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:
0.0000190
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 30, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.247C>G (p.L83V) alteration is located in exon 3 (coding exon 2) of the CA5B gene. This alteration results from a C to G substitution at nucleotide position 247, causing the leucine (L) at amino acid position 83 to be replaced by a valine (V). 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
0.19
BayesDel_addAF
Benign
-0.022
T
BayesDel_noAF
Benign
-0.27
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.30
T;.;T
FATHMM_MKL
Uncertain
0.76
D
LIST_S2
Benign
0.82
.;T;T
M_CAP
Benign
0.031
D
MetaRNN
Uncertain
0.72
D;D;D
MetaSVM
Benign
-0.29
T
MutationAssessor
Uncertain
2.5
M;.;M
PrimateAI
Uncertain
0.56
T
PROVEAN
Benign
-2.3
N;D;N
REVEL
Uncertain
0.51
Sift
Benign
0.033
D;D;D
Sift4G
Uncertain
0.0040
D;D;D
Polyphen
0.97
D;.;D
Vest4
0.43
MutPred
0.74
Gain of methylation at K81 (P = 0.0628);Gain of methylation at K81 (P = 0.0628);Gain of methylation at K81 (P = 0.0628);
MVP
0.84
MPC
2.5
ClinPred
0.96
D
GERP RS
4.5
Varity_R
0.39
gMVP
0.72

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: rs1379030882; hg19: chrX-15782805; API