NM_000500.9:c.37C>A
Variant names:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_000500.9(CYP21A2):c.37C>A(p.Leu13Met) 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 benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
CYP21A2
NM_000500.9 missense
NM_000500.9 missense
Scores
1
4
12
Clinical Significance
Conservation
PhyloP100: -0.757
Genes affected
CYP21A2 (HGNC:2600): (cytochrome P450 family 21 subfamily A 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 endoplasmic reticulum and hydroxylates steroids at the 21 position. Its activity is required for the synthesis of steroid hormones including cortisol and aldosterone. Mutations in this gene cause congenital adrenal hyperplasia. A related pseudogene is located near this gene; gene conversion events involving the functional gene and the pseudogene are thought to account for many cases of steroid 21-hydroxylase deficiency. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.38025612).
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0AN: 1413158Hom.: 0 Cov.: 104 AF XY: 0.00 AC XY: 0AN XY: 698660
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
AC:
0
AN:
1413158
Hom.:
Cov.:
104
AF XY:
AC XY:
0
AN XY:
698660
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency Uncertain:1
Jan 20, 2023
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing
ACMG classification criteria: PM2 moderated, BP4 supporting -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
.;.;.;T;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
.;.;T;T;.;.
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;N;N;N;.
REVEL
Uncertain
Sift
Pathogenic
D;.;D;D;D;.
Sift4G
Uncertain
D;.;D;D;D;.
Polyphen
D;D;.;.;.;D
Vest4
MutPred
Gain of MoRF binding (P = 0.0809);Gain of MoRF binding (P = 0.0809);Gain of MoRF binding (P = 0.0809);Gain of MoRF binding (P = 0.0809);Gain of MoRF binding (P = 0.0809);Gain of MoRF binding (P = 0.0809);
MVP
MPC
ClinPred
T
GERP RS
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
No publications associated with this variant yet.