rs606231136

Positions:

• chr9-137452600-CAGGCCACAA-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001130969.3(NSMF):​c.1132-23_1132-15del variant causes a splice polypyrimidine tract, intron 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 risk factor (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NSMF NM_001130969.3 splice_polypyrimidine_tract, intron
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: 2.35

Genes affected

NSMF (HGNC:29843): (NMDA receptor synaptonuclear signaling and neuronal migration factor) The protein encoded by this gene is involved in guidance of olfactory axon projections and migration of luteinizing hormone-releasing hormone neurons. Defects in this gene are a cause of idiopathic hypogonadotropic hypogonadism (IHH). Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NSMF	NM_001130969.3	c.1132-23_1132-15del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000371475.9	NP_001124441.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NSMF	ENST00000371475.9	c.1132-23_1132-15del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001130969.3	ENSP00000360530	A1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Hypogonadotropic hypogonadism 9 with or without anosmia Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Feb 01, 2007

- -

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: rs606231136; hg19: chr9-140347052;