GNRH1 p.Phe61Phe

Variant names:

• chr8-25421626-C-C
• NM_001083111.2:c.

Your query was ambiguous. Multiple possible variants found:

• chr8-25421627--
• chr8-25421627-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001083111.2(GNRH1):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: GNRH1 NM_001083111.2 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.82
• Publications: 0 publications found

Genes affected

GNRH1 (HGNC:4419): (gonadotropin releasing hormone 1) This gene encodes a preproprotein that is proteolytically processed to generate a peptide that is a member of the gonadotropin-releasing hormone (GnRH) family of peptides. Alternative splicing results in multiple transcript variants, at least one of which is secreted and then cleaved to generate gonadoliberin-1 and GnRH-associated peptide 1. Gonadoliberin-1 stimulates the release of luteinizing and follicle stimulating hormones, which are important for reproduction. Mutations in this gene are associated with hypogonadotropic hypogonadism. [provided by RefSeq, Nov 2015]

GNRH1 Gene-Disease associations (from GenCC):

• hypogonadotropic hypogonadism 12 with or without anosmia

  Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• hypogonadotropic hypogonadism

  Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001083111.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNRH1	NM_001083111.2	MANE Select	c.		exon_region	Exon 3 of 4	NP_001076580.1	P01148
	GNRH1	NM_000825.3		c.		exon_region	Exon 2 of 3	NP_000816.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNRH1	ENST00000421054.7	TSL:1 MANE Select	c.		exon_region	Exon 3 of 4	ENSP00000391280.2	P01148
	GNRH1	ENST00000276414.4	TSL:1	c.		exon_region	Exon 2 of 3	ENSP00000276414.4	P01148
	GNRH1	ENST00000966630.1		c.		exon_region	Exon 3 of 4	ENSP00000636689.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-3.8

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr8-25279142;