rs72547508
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PP3_StrongPP5_Moderate
The NM_000781.3(CYP11A1):c.1057C>T(p.Arg353Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,613,950 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R353Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_000781.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CYP11A1 | NM_000781.3 | c.1057C>T | p.Arg353Trp | missense_variant | 6/9 | ENST00000268053.11 | |
CYP11A1 | NM_001099773.2 | c.583C>T | p.Arg195Trp | missense_variant | 6/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CYP11A1 | ENST00000268053.11 | c.1057C>T | p.Arg353Trp | missense_variant | 6/9 | 1 | NM_000781.3 | P1 | |
CYP11A1 | ENST00000358632.8 | c.583C>T | p.Arg195Trp | missense_variant | 6/9 | 2 | |||
CYP11A1 | ENST00000566674.5 | c.583C>T | p.Arg195Trp | missense_variant | 6/6 | 5 | |||
CYP11A1 | ENST00000435365.5 | c.1057C>T | p.Arg353Trp | missense_variant, NMD_transcript_variant | 6/8 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152074Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251368Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135858
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461876Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 727236
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152074Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74282
ClinVar
Submissions by phenotype
Congenital adrenal insufficiency with 46, XY sex reversal OR 46,XY disorder of sex development-adrenal insufficiency due to CYP11A1 deficiency Pathogenic:2
Likely pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Nov 30, 2021 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Aug 01, 2002 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at