X-15764583-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_007220.4(CA5B):​c.148C>A​(p.Pro50Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000913 in 1,095,140 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P50A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 21)
Exomes 𝑓: 9.1e-7 ( 0 hom. 1 hem. )

Consequence

CA5B
NM_007220.4 missense

Scores

5
9
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.83
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 Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.817

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CA5BNM_007220.4 linkc.148C>A p.Pro50Thr missense_variant Exon 3 of 8 ENST00000318636.8 NP_009151.1 Q9Y2D0A0A024RBW9
CA5BP1-CA5BNR_160544.1 linkn.912C>A non_coding_transcript_exon_variant Exon 6 of 12
CA5BP1-CA5BNR_160545.1 linkn.912C>A 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.148C>A p.Pro50Thr missense_variant Exon 3 of 8 1 NM_007220.4 ENSP00000314099.3 Q9Y2D0

Frequencies

GnomAD3 genomes
Cov.:
21
GnomAD3 exomes
AF:
0.00000557
AC:
1
AN:
179602
Hom.:
0
AF XY:
0.0000155
AC XY:
1
AN XY:
64418
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:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000125
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
9.13e-7
AC:
1
AN:
1095140
Hom.:
0
Cov.:
31
AF XY:
0.00000277
AC XY:
1
AN XY:
360974
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:
0.00000119
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.39
BayesDel_addAF
Uncertain
0.16
D
BayesDel_noAF
Uncertain
-0.010
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.18
.;T;.;T
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.81
T;.;T;T
M_CAP
Uncertain
0.10
D
MetaRNN
Pathogenic
0.82
D;D;D;D
MetaSVM
Uncertain
-0.18
T
MutationAssessor
Uncertain
2.2
.;M;.;M
PrimateAI
Uncertain
0.67
T
PROVEAN
Pathogenic
-7.8
D;D;D;D
REVEL
Uncertain
0.52
Sift
Pathogenic
0.0
D;D;D;D
Sift4G
Pathogenic
0.0
D;D;D;D
Polyphen
1.0
.;D;.;D
Vest4
0.70, 0.70
MutPred
0.61
Gain of MoRF binding (P = 0.0854);Gain of MoRF binding (P = 0.0854);Gain of MoRF binding (P = 0.0854);Gain of MoRF binding (P = 0.0854);
MVP
0.76
MPC
0.93
ClinPred
0.98
D
GERP RS
5.2
Varity_R
0.57
gMVP
0.75

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
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: rs138875072; hg19: chrX-15782706; API