NM_001217.5:c.22A>G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001217.5(CA11):​c.22A>G​(p.Ser8Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000282 in 1,598,458 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 0.000059 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

CA11
NM_001217.5 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.40
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]
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.11401275).
BS2
High AC in GnomAd4 at 9 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CA11NM_001217.5 linkc.22A>G p.Ser8Gly missense_variant Exon 1 of 9 ENST00000084798.9 NP_001208.2 O75493
CA11NR_136241.2 linkn.577A>G non_coding_transcript_exon_variant Exon 1 of 9
SEC1PNR_004401.2 linkn.108+7465T>C intron_variant Intron 1 of 4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CA11ENST00000084798.9 linkc.22A>G p.Ser8Gly missense_variant Exon 1 of 9 1 NM_001217.5 ENSP00000084798.3 O75493
SEC1PENST00000474419.5 linkn.76+7465T>C intron_variant Intron 1 of 3 1
SEC1PENST00000483163.1 linkn.76+7465T>C intron_variant Intron 1 of 1 1
SEC1PENST00000430145.3 linkn.48+7465T>C intron_variant Intron 1 of 4 2

Frequencies

GnomAD3 genomes
AF:
0.0000595
AC:
9
AN:
151328
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000487
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:
0.000103
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000249
AC:
36
AN:
1447130
Hom.:
0
Cov.:
33
AF XY:
0.0000167
AC XY:
12
AN XY:
718574
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:
0.0000308
Gnomad4 OTH exome
AF:
0.0000335
GnomAD4 genome
AF:
0.0000595
AC:
9
AN:
151328
Hom.:
0
Cov.:
31
AF XY:
0.0000541
AC XY:
4
AN XY:
73920
show subpopulations
Gnomad4 AFR
AF:
0.0000487
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:
0.000103
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000416
ExAC
AF:
0.0000165
AC:
2

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
May 05, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.22A>G (p.S8G) alteration is located in exon 1 (coding exon 1) of the CA11 gene. This alteration results from a A to G substitution at nucleotide position 22, causing the serine (S) at amino acid position 8 to be replaced by a glycine (G). 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
0.065
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.41
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.033
T
Eigen
Benign
-0.49
Eigen_PC
Benign
-0.32
FATHMM_MKL
Benign
0.41
N
LIST_S2
Benign
0.69
T
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.11
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N
PrimateAI
Uncertain
0.68
T
PROVEAN
Benign
-0.65
N
REVEL
Benign
0.048
Sift
Uncertain
0.0050
D
Sift4G
Benign
0.40
T
Polyphen
0.0
B
Vest4
0.16
MutPred
0.30
Loss of glycosylation at S8 (P = 0.0135);
MVP
0.43
MPC
1.2
ClinPred
0.39
T
GERP RS
3.0
Varity_R
0.095
gMVP
0.53

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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: rs765428646; hg19: chr19-49148868; API