chr15-63326293-G-A

Position:

chr15-63326293-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001218.5(CA12):c.1057C>T(p.His353Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000254 in 1,613,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

CA12
NM_001218.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.120

Variant links:

Genes affected

CA12 (HGNC:1371): (carbonic anhydrase 12) 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. This gene product is a type I membrane protein that is highly expressed in normal tissues, such as kidney, colon and pancreas, and has been found to be overexpressed in 10% of clear cell renal carcinomas. Three transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jun 2014]

CA12 links:

LOC124903506 (HGNC:):

LOC124903506 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.061957806).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CA12	NM_001218.5 linkuse as main transcript	c.1057C>T	p.His353Tyr	missense_variant	11/11	ENST00000178638.8
LOC124903506	XR_007064676.1 linkuse as main transcript	n.767+7539G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CA12	ENST00000178638.8 linkuse as main transcript	c.1057C>T	p.His353Tyr	missense_variant	11/11	1	NM_001218.5	A1	O43570-1
CA12	ENST00000344366.7 linkuse as main transcript	c.1024C>T	p.His342Tyr	missense_variant	10/10	1		P4	O43570-2
CA12	ENST00000422263.2 linkuse as main transcript	c.844C>T	p.His282Tyr	missense_variant	9/9	2
CA12	ENST00000560666.1 linkuse as main transcript	n.267C>T		non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000483

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000358

AC:

AN:

251388

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.000554

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000144

AC:

AN:

1461598

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

727136

show subpopulations

Gnomad4 AFR exome

AF:

0.000508

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:

0.00000180

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.000131

AC:

AN:

152268

Hom.:

Cov.:

AF XY:

0.0000940

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000481

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000132

Hom.:

Bravo

AF:

0.000166

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000247

AC:

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 submitter

clinical testing

Ambry Genetics

Jul 08, 2022

The c.1057C>T (p.H353Y) alteration is located in exon 11 (coding exon 11) of the CA12 gene. This alteration results from a C to T substitution at nucleotide position 1057, causing the histidine (H) at amino acid position 353 to be replaced by a tyrosine (Y). 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

0.076

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

T;.;.

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.095

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.46

T;T;T

M_CAP

Benign

0.037

MetaRNN

Benign

0.062

T;T;T

MetaSVM

Benign

-0.73

MutationAssessor

Uncertain

2.1

M;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.1

N;N;N

REVEL

Benign

0.098

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.024

B;B;B

Vest4

0.22

MVP

0.78

MPC

0.36

ClinPred

0.23

GERP RS

2.6

Varity_R

0.13

gMVP

0.32

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over