rs121918656
Variant summary
Our verdict is Pathogenic. Variant got 13 ACMG points: 13P and 0B. PVS1PS1_ModeratePM2PP5
The NM_004959.5(NR5A1):c.3G>A(p.Met1?) variant causes a start lost change. 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 Pathogenic (no stars).
Frequency
Genomes: not found (cov: 33)
Consequence
NR5A1
NM_004959.5 start_lost
NM_004959.5 start_lost
Scores
6
5
1
Clinical Significance
Conservation
PhyloP100: 5.89
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 Pathogenic. Variant got 13 ACMG points.
PVS1
?
Start lost variant, no new inframe start found.
PS1
?
Another start lost variant in NM_004959.5 (NR5A1) was described as [Pathogenic] in Lovd
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 9-124503393-C-T is Pathogenic according to our data. Variant chr9-124503393-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 12806.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr9-124503393-C-T is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NR5A1 | NM_004959.5 | c.3G>A | p.Met1? | start_lost | 2/7 | ENST00000373588.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NR5A1 | ENST00000373588.9 | c.3G>A | p.Met1? | start_lost | 2/7 | 1 | NM_004959.5 | P1 | |
NR5A1 | ENST00000620110.4 | c.3G>A | p.Met1? | start_lost | 2/6 | 5 | |||
NR5A1 | ENST00000455734.1 | c.3G>A | p.Met1? | start_lost | 2/4 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Premature ovarian failure 7 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 19, 2009 | - - |
46,XY sex reversal 3 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 19, 2009 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Pathogenic
D
MutationTaster
Benign
A
Sift4G
Uncertain
D;D;.
Polyphen
0.94
.;P;.
Vest4
MutPred
Gain of catalytic residue at M1 (P = 0.0542);Gain of catalytic residue at M1 (P = 0.0542);Gain of catalytic residue at M1 (P = 0.0542);
MVP
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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