19-48639563-C-T

Variant names:

Variant summary

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

The NM_001217.5(CA11):c.626G>A(p.Arg209His) variant causes a missense change. The variant allele was found at a frequency of 0.0000806 in 1,613,800 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000084 ( 0 hom. )

Consequence

CA11
NM_001217.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.68

Variant links:

Genes affected

CA11 (HGNC:1370): (carbonic anhydrase 11) 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. CA XI is likely a secreted protein, however, radical changes at active site residues completely conserved in CA isozymes with catalytic activity, make it unlikely that it has carbonic anhydrase activity. It shares properties in common with two other acatalytic CA isoforms, CA VIII and CA X. CA XI is most abundantly expressed in brain, and may play a general role in the central nervous system. [provided by RefSeq, Jul 2008]

CA11 links:

SEC1P (HGNC:44149): (secretory blood group 1, pseudogene) Predicted to enable galactoside 2-alpha-L-fucosyltransferase activity. Predicted to act upstream of or within protein glycosylation. [provided by Alliance of Genome Resources, Apr 2022]

SEC1P links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CA11	NM_001217.5 link	c.626G>A	p.Arg209His	missense_variant	Exon 6 of 9	ENST00000084798.9	NP_001208.2	O75493
CA11	NR_136241.2 link	n.1181G>A		non_coding_transcript_exon_variant	Exon 6 of 9
SEC1P	NR_004401.2 link	n.108+1417C>T		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CA11	ENST00000084798.9 link	c.626G>A	p.Arg209His	missense_variant	Exon 6 of 9	1	NM_001217.5	ENSP00000084798.3		O75493

Frequencies

GnomAD3 genomes

AF:

0.0000461

AC:

AN:

151966

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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:

0.0000883

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000278

AC:

AN:

251414

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135876

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:

0.0000615

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000841

AC:

123

AN:

1461834

Hom.:

Cov.:

AF XY:

0.0000839

AC XY:

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

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:

0.000102

Gnomad4 OTH exome

AF:

0.000132

GnomAD4 genome

AF:

0.0000461

AC:

AN:

151966

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74218

show subpopulations

Gnomad4 AFR

AF:

0.0000242

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:

0.0000883

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000135

Hom.:

Bravo

AF:

0.0000680

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 20, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.626G>A (p.R209H) alteration is located in exon 6 (coding exon 6) of the CA11 gene. This alteration results from a G to A substitution at nucleotide position 626, causing the arginine (R) at amino acid position 209 to be replaced by a histidine (H). 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

0.28

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.25

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.084

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.89

LIST_S2

Pathogenic

0.99

M_CAP

Uncertain

0.16

MetaRNN

Uncertain

0.42

MetaSVM

Benign

-0.59

MutationAssessor

Benign

1.5

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.22

Sift

Benign

0.070

Sift4G

Benign

0.061

Polyphen

0.89

Vest4

0.55

MutPred

0.41

Loss of MoRF binding (P = 0.0876);

MVP

0.57

MPC

1.9

ClinPred

0.58

GERP RS

3.3

Varity_R

0.099

gMVP

0.57

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