rs606231208

Positions:

• chr9-124500260-CCAGCTGCAG-C

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1 PM2 PM4 PP5

The ENST00000373588.9(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 ENST00000373588.9 inframe_deletion
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 6.94

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PM1: In a region_of_interest Important for dimerization (size 231) in uniprot entity STF1_HUMAN there are 48 pathogenic changes around while only 0 benign (100%) in ENST00000373588.9
• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in ENST00000373588.9.
• PP5: 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	Protein	UniProt
NR5A1	NM_004959.5	c.691_699del	p.Leu231_Leu233del	inframe_deletion	4/7	ENST00000373588.9	NP_004950.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR5A1	ENST00000373588.9	c.691_699del	p.Leu231_Leu233del	inframe_deletion	4/7	1	NM_004959.5	ENSP00000362690	P1
NR5A1	ENST00000373587.3	c.43_51del	p.Leu15_Leu17del	inframe_deletion	2/5	3		ENSP00000362689
NR5A1	ENST00000620110.4	c.691_699del	p.Leu231_Leu233del	inframe_deletion	4/6	5		ENSP00000483309

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Premature ovarian failure 7 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Mar 19, 2009

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs606231208; hg19: chr9-127262539;