rs766788186

Variant summary

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

The NM_001128831.4(CA1):ā€‹c.770T>Gā€‹(p.Val257Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000689 in 1,451,780 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.9e-7 ( 0 hom. )

Consequence

CA1
NM_001128831.4 missense

Scores

12
4
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.29
Variant links:
Genes affected
CA1 (HGNC:1368): (carbonic anhydrase 1) 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 CA1 gene is closely linked to the CA2 and CA3 genes on chromosome 8. It encodes a cytosolic protein that is found at the highest level in erythrocytes. Allelic variants of this gene have been described in some populations. Alternative splicing and the use of alternative promoters results in multiple transcript variants. [provided by RefSeq, Nov 2016]

Genome browser will be placed here

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, 0.957

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CA1NM_001128831.4 linkc.770T>G p.Val257Gly missense_variant Exon 8 of 8 ENST00000523022.6 NP_001122303.1 P00915V9HWE3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CA1ENST00000523022.6 linkc.770T>G p.Val257Gly missense_variant Exon 8 of 8 1 NM_001128831.4 ENSP00000429798.1 P00915

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.89e-7
AC:
1
AN:
1451780
Hom.:
0
Cov.:
28
AF XY:
0.00000138
AC XY:
1
AN XY:
722838
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.91
BayesDel_addAF
Pathogenic
0.38
D
BayesDel_noAF
Pathogenic
0.31
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.34
T;T;T;T;T;T;T
Eigen
Pathogenic
0.85
Eigen_PC
Pathogenic
0.69
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.92
.;.;.;.;D;D;D
M_CAP
Uncertain
0.17
D
MetaRNN
Pathogenic
0.96
D;D;D;D;D;D;D
MetaSVM
Uncertain
0.70
D
MutationAssessor
Pathogenic
4.8
.;H;H;H;H;.;.
PrimateAI
Benign
0.37
T
PROVEAN
Pathogenic
-6.3
.;D;D;D;D;D;D
REVEL
Pathogenic
0.82
Sift
Pathogenic
0.0
.;D;D;D;D;D;D
Sift4G
Pathogenic
0.0
D;D;D;D;D;D;.
Polyphen
1.0
.;D;D;D;D;.;.
Vest4
0.81
MutPred
0.79
.;Loss of stability (P = 0.0123);Loss of stability (P = 0.0123);Loss of stability (P = 0.0123);Loss of stability (P = 0.0123);.;.;
MVP
0.95
MPC
0.25
ClinPred
1.0
D
GERP RS
4.7
Varity_R
0.99
gMVP
0.88

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: rs766788186; hg19: chr8-86240805; API