Menu
GeneBe

rs606231208

chr9-124500260-CCAGCTGCAG-C

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PM2PM4PP5

The NM_004959.5(NR5A1):c.691_699del(p.Leu231_Leu233del) variant causes a inframe deletion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 33)

Consequence

NR5A1
NM_004959.5 inframe_deletion

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 6.94
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

PM1
?
    PM1 - Located in a mutational hot spot and/or critical and well-established functional domain (e.g., active site of an enzyme) without benign variation
In a domain NR LBD (size 237) in uniprot entity STF1_HUMAN there are 48 pathogenic changes around while only 0 benign (100%) in NM_004959.5
PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
PM4
?
    PM4 - Protein length changes as a result of in-frame deletions/insertions in a nonrepeat region or stop-loss variants
Nonframeshift variant in NON repetitive region in NM_004959.5.
PP5
?
    PP5 - Reputable source recently reports variant as pathogenic, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 9-124500260-CCAGCTGCAG-C is Pathogenic according to our data. Variant chr9-124500260-CCAGCTGCAG-C is described in ClinVar as [Pathogenic]. Clinvar id is 12808.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr9-124500260-CCAGCTGCAG-C is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NR5A1NM_004959.5 linkuse as main transcriptc.691_699del p.Leu231_Leu233del inframe_deletion 4/7 ENST00000373588.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NR5A1ENST00000373588.9 linkuse as main transcriptc.691_699del p.Leu231_Leu233del inframe_deletion 4/71 NM_004959.5 P1
NR5A1ENST00000373587.3 linkuse as main transcriptc.43_51del p.Leu15_Leu17del inframe_deletion 2/53
NR5A1ENST00000620110.4 linkuse as main transcriptc.691_699del p.Leu231_Leu233del inframe_deletion 4/65

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
Cov.:
33
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
Cov.:
33

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Premature ovarian failure 7 Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMMar 19, 2009- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs606231208; hg19: chr9-127262539; API