chr9-124482878-G-A
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6BP7
The NM_004959.5(NR5A1):c.1266C>T(p.Cys422=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000291 in 1,614,178 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00016 ( 0 hom., cov: 30)
Exomes 𝑓: 0.000016 ( 0 hom. )
Consequence
NR5A1
NM_004959.5 synonymous
NM_004959.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.02
Genes affected
NR5A1 (HGNC:7983): (nuclear receptor subfamily 5 group A member 1) The protein encoded by this gene is a transcriptional activator involved in sex determination. The encoded protein binds DNA as a monomer. Defects in this gene are a cause of XY sex reversal with or without adrenal failure as well as adrenocortical insufficiency without ovarian defect. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.48).
BP6
Variant 9-124482878-G-A is Benign according to our data. Variant chr9-124482878-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 598335.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
BP7
Synonymous conserved (PhyloP=2.02 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NR5A1 | NM_004959.5 | c.1266C>T | p.Cys422= | synonymous_variant | 7/7 | ENST00000373588.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NR5A1 | ENST00000373588.9 | c.1266C>T | p.Cys422= | synonymous_variant | 7/7 | 1 | NM_004959.5 | P1 | |
NR5A1 | ENST00000620110.4 | c.1146C>T | p.Cys382= | synonymous_variant | 6/6 | 5 | |||
NR5A1 | ENST00000373587.3 | c.618C>T | p.Cys206= | synonymous_variant | 5/5 | 3 |
Frequencies
GnomAD3 genomes AF: 0.000158 AC: 24AN: 152194Hom.: 0 Cov.: 30
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GnomAD3 exomes AF: 0.0000478 AC: 12AN: 251290Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135854
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GnomAD4 exome AF: 0.0000157 AC: 23AN: 1461866Hom.: 0 Cov.: 37 AF XY: 0.0000193 AC XY: 14AN XY: 727234
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GnomAD4 genome AF: 0.000158 AC: 24AN: 152312Hom.: 0 Cov.: 30 AF XY: 0.000121 AC XY: 9AN XY: 74464
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 20, 2018 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jul 17, 2019 | - - |
Computational scores
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BayesDel_noAF
Benign
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Benign
DANN
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at