rs587781103

chr9-137459023-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Moderate BP6_Very_Strong BS2

The NM_001130969.3(NSMF):c.71+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00275 in 1,280,446 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0012 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0030 (4 hom.)
• Consequence: NSMF NM_001130969.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.456

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 9-137459023-C-T is Benign according to our data. Variant chr9-137459023-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 138563.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd at 190 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NSMF	NM_001130969.3	c.71+9G>A		intron_variant		ENST00000371475.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NSMF	ENST00000371475.9	c.71+9G>A		intron_variant		1	NM_001130969.3	A1

Frequencies

GnomAD3 genomes AF: 0.00125 AC: 190 AN: 151918 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000459

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000379

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00230

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00221 AC: 17 AN: 7698 Hom.: 0 AF XY: 0.00108 AC XY: 5 AN XY: 4620

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00245

Gnomad ASJ exome AF: 0.00145

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00485

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00295 AC: 3331 AN: 1128420 Hom.: 4 Cov.: 30 AF XY: 0.00289 AC XY: 1561 AN XY: 539712

Gnomad4 AFR exome AF: 0.000438

Gnomad4 AMR exome AF: 0.000730

Gnomad4 ASJ exome AF: 0.0000649

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000285

Gnomad4 NFE exome AF: 0.00334

Gnomad4 OTH exome AF: 0.00302

GnomAD4 genome AF: 0.00125 AC: 190 AN: 152026 Hom.: 0 Cov.: 33 AF XY: 0.00109 AC XY: 81 AN XY: 74344

Gnomad4 AFR AF: 0.000458

Gnomad4 AMR AF: 0.000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000379

Gnomad4 NFE AF: 0.00230

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00122 Hom.: 0

Bravo AF: 0.00134

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 04, 2013	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Dec 09, 2016	- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jun 30, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
Cadd	Benign	6.8
Dann	Benign	0.97
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs587781103; hg19: chr9-140353475;