rs72554626
Variant names:
Variant summary
Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PM2PP3_StrongPP5_Moderate
The NM_000498.3(CYP11B2):c.1492A>G(p.Thr498Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
CYP11B2
NM_000498.3 missense
NM_000498.3 missense
Scores
3
8
7
Clinical Significance
Conservation
PhyloP100: 2.81
Publications
6 publications found
Genes affected
CYP11B2 (HGNC:2592): (cytochrome P450 family 11 subfamily B member 2) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the mitochondrial inner membrane. The enzyme has steroid 18-hydroxylase activity to synthesize aldosterone and 18-oxocortisol as well as steroid 11 beta-hydroxylase activity. Mutations in this gene cause corticosterone methyl oxidase deficiency. [provided by RefSeq, Jul 2008]
GML (HGNC:4375): (glycosylphosphatidylinositol anchored molecule like) Predicted to be involved in DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest; apoptotic process; and negative regulation of cell population proliferation. Predicted to be extrinsic component of membrane. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification was made for transcript
Our verdict: Likely_pathogenic. The variant received 8 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.976
PP5
Variant 8-142912000-T-C is Pathogenic according to our data. Variant chr8-142912000-T-C is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 16885.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_000498.3. You can select a different transcript below to see updated ACMG assignments.
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CYP11B2 | TSL:1 MANE Select | c.1492A>G | p.Thr498Ala | missense | Exon 9 of 9 | ENSP00000325822.2 | P19099 | ||
| CYP11B2 | c.1561A>G | p.Thr521Ala | missense | Exon 9 of 9 | ENSP00000615954.1 | ||||
| CYP11B2 | c.1480A>G | p.Thr494Ala | missense | Exon 9 of 9 | ENSP00000615955.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
GnomAD4 genome
Cov.:
32
Alfa
AF:
Hom.:
ClinVar
ClinVar submissions
View on ClinVar Significance:Likely pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
1
-
-
Corticosterone methyloxidase type 2 deficiency (1)
1
-
-
CYP11B2-related disorder (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
DANN
Uncertain
DEOGEN2
Uncertain
D
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M
PhyloP100
PrimateAI
Benign
T
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Loss of sheet (P = 0.0817)
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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