9-137459023-C-G

Variant names:

• chr9-137459023-C-G
• rs587781103
• NM_001130969.3:c.71+9G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001130969.3(NSMF):​c.71+9G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000886 in 1,128,442 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 8.9e-7 (0 hom.)
• Consequence: NSMF NM_001130969.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.456
• Publications: 0 publications found

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]

NSMF Gene-Disease associations (from GenCC):

• hypogonadotropic hypogonadism 9 with or without anosmia

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

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NSMF	NM_001130969.3	c.71+9G>C		intron_variant	Intron 1 of 15	ENST00000371475.9	NP_001124441.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NSMF	ENST00000371475.9	c.71+9G>C		intron_variant	Intron 1 of 15	1	NM_001130969.3	ENSP00000360530.3
NSMF	ENST00000371472.6	c.71+9G>C		intron_variant	Intron 1 of 15	2		ENSP00000360527.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.86e-7 AC: 1 AN: 1128442 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 539724

African (AFR) AF: 0.00 AC: 0 AN: 22806

American (AMR) AF: 0.00 AC: 0 AN: 9586

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15410

East Asian (EAS) AF: 0.00 AC: 0 AN: 25884

South Asian (SAS) AF: 0.00 AC: 0 AN: 34294

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24530

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3070

European-Non Finnish (NFE) AF: 0.00000106 AC: 1 AN: 947172

Other (OTH) AF: 0.00 AC: 0 AN: 45690

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	6.4
DANN	Benign	0.87
PhyloP100		-0.46
PromoterAI		-0.018	Neutral

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

Other links and lift over

dbSNP: rs587781103; hg19: chr9-140353475;