rs587777740

Positions:

• chr7-122303784-GA-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_001024613.4(FEZF1):​c.653del​(p.Phe218SerfsTer13) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FEZF1 NM_001024613.4 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 2.92

Genes affected

FEZF1 (HGNC:22788): (FEZ family zinc finger 1) This gene encodes a transcriptional repressor that belongs to the zinc finger double domain protein family. The encoded protein is thought to play a role in the embryonic migration of gonadotropin-releasing hormone neurons into the brain. Mutations in this gene are associated with hypogonadotropic hypogonadism-22 with anosmia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2014]

FEZF1-AS1 (HGNC:41001): (FEZF1 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 7-122303784-GA-G is Pathogenic according to our data. Variant chr7-122303784-GA-G is described in ClinVar as [Pathogenic]. Clinvar id is 156220.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FEZF1	NM_001024613.4	c.653del	p.Phe218SerfsTer13	frameshift_variant	1/4	ENST00000442488.7	NP_001019784.2
FEZF1-AS1	NR_036484.1	n.130del		non_coding_transcript_exon_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FEZF1	ENST00000442488.7	c.653del	p.Phe218SerfsTer13	frameshift_variant	1/4	1	NM_001024613.4	ENSP00000411145	P2
FEZF1	ENST00000427185.2	c.503del	p.Phe168SerfsTer13	frameshift_variant	2/5	1		ENSP00000392727	A2
FEZF1-AS1	ENST00000428449.5	n.130del		non_coding_transcript_exon_variant	1/7	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Hypogonadotropic hypogonadism 22 with anosmia Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Sep 04, 2014

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs587777740; hg19: chr7-121943838;