rs200749741
Positions:
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS1
The NM_004959.5(NR5A1):c.386C>T(p.Pro129Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000172 in 1,612,092 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00083 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00010 ( 1 hom. )
Consequence
NR5A1
NM_004959.5 missense
NM_004959.5 missense
Scores
4
10
Clinical Significance
Conservation
PhyloP100: 3.73
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 Benign. Variant got -16 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.047962666).
BP6
?
Variant 9-124500574-G-A is Benign according to our data. Variant chr9-124500574-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 242720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000834 (127/152328) while in subpopulation AFR AF= 0.00265 (110/41574). AF 95% confidence interval is 0.00224. There are 0 homozygotes in gnomad4. There are 63 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NR5A1 | NM_004959.5 | c.386C>T | p.Pro129Leu | missense_variant | 4/7 | ENST00000373588.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NR5A1 | ENST00000373588.9 | c.386C>T | p.Pro129Leu | missense_variant | 4/7 | 1 | NM_004959.5 | P1 | |
NR5A1 | ENST00000620110.4 | c.386C>T | p.Pro129Leu | missense_variant | 4/6 | 5 | |||
NR5A1 | ENST00000455734.1 | c.386C>T | p.Pro129Leu | missense_variant | 4/4 | 3 | |||
NR5A1 | ENST00000373587.3 | c.40-302C>T | intron_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.000821 AC: 125AN: 152210Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000228 AC: 55AN: 241048Hom.: 1 AF XY: 0.000151 AC XY: 20AN XY: 132448
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GnomAD4 exome AF: 0.000103 AC: 151AN: 1459764Hom.: 1 Cov.: 32 AF XY: 0.0000868 AC XY: 63AN XY: 726176
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GnomAD4 genome ? AF: 0.000834 AC: 127AN: 152328Hom.: 0 Cov.: 33 AF XY: 0.000846 AC XY: 63AN XY: 74478
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Oligosynaptic infertility;C2751824:46,XY disorder of sex development Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 14, 2023 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 11, 2021 | In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 20887963, 23543655, 32242295, 31787151) - |
NR5A1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 09, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
D;T;T
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Uncertain
D
MutationTaster
Benign
A
PrimateAI
Benign
T
Sift4G
Benign
T;T;.
Polyphen
0.35
.;B;.
Vest4
MVP
MPC
0.76
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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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