chr9-124500260-CCAGCTGCAG-C

Variant names:

• chr9-124500260-CCAGCTGCAG-C
• rs606231208
• NM_004959.5:c.691_699delCTGCAGCTG

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PM4 PP5

The NM_004959.5(NR5A1):​c.691_699delCTGCAGCTG​(p.Leu231_Leu233del) variant causes a conservative 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 conservative_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 Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_004959.5.
• 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 rank	MANE	Protein	UniProt
NR5A1	NM_004959.5	c.691_699delCTGCAGCTG	p.Leu231_Leu233del	conservative_inframe_deletion	Exon 4 of 7	ENST00000373588.9	NP_004950.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR5A1	ENST00000373588.9	c.691_699delCTGCAGCTG	p.Leu231_Leu233del	conservative_inframe_deletion	Exon 4 of 7	1	NM_004959.5	ENSP00000362690.4
NR5A1	ENST00000620110.4	c.691_699delCTGCAGCTG	p.Leu231_Leu233del	conservative_inframe_deletion	Exon 4 of 6	5		ENSP00000483309.1
NR5A1	ENST00000373587.3	c.43_51delCTGCAGCTG	p.Leu15_Leu17del	conservative_inframe_deletion	Exon 2 of 5	3		ENSP00000362689.3
NR5A1	ENST00000455734.1	c.*158_*166delCTGCAGCTG		downstream_gene_variant		3		ENSP00000393245.1

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

Mar 19, 2009

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

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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;