chr9-137449752-C-T

Variant names:

• chr9-137449752-C-T
• rs41309970
• NM_001130969.3:c.1420-78G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001130969.3(NSMF):​c.1420-78G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 1,392,130 control chromosomes in the GnomAD database, including 74,795 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (6005 hom., cov: 32)
  • Exomes 𝑓: 0.33 (68790 hom.)
• Consequence: NSMF NM_001130969.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.519
• Publications: 7 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 9-137449752-C-T is Benign according to our data. Variant chr9-137449752-C-T is described in ClinVar as Benign. ClinVar VariationId is 673329.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130969.3. 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
	NSMF	NM_001130969.3	MANE Select	c.1420-78G>A		intron	N/A	NP_001124441.1	Q6X4W1-1
	NSMF	NM_015537.5		c.1414-78G>A		intron	N/A	NP_056352.3
	NSMF	NM_001130970.2		c.1351-78G>A		intron	N/A	NP_001124442.1	Q6X4W1-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NSMF	ENST00000371475.9	TSL:1 MANE Select	c.1420-78G>A		intron	N/A	ENSP00000360530.3	Q6X4W1-1
	NSMF	ENST00000265663.12	TSL:1	c.1414-78G>A		intron	N/A	ENSP00000265663.7	Q6X4W1-2
	NSMF	ENST00000371472.6	TSL:2	c.1414-78G>A		intron	N/A	ENSP00000360527.1	Q6X4W1-2

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39378 AN: 151838 Hom.: 6004 Cov.: 32

Gnomad AFR AF: 0.0969

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.258

GnomAD4 exome AF: 0.326 AC: 404016 AN: 1240174 Hom.: 68790 Cov.: 17 AF XY: 0.327 AC XY: 203939 AN XY: 623750

African (AFR) AF: 0.0865 AC: 2507 AN: 28990

American (AMR) AF: 0.291 AC: 11013 AN: 37854

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 7344 AN: 24414

East Asian (EAS) AF: 0.157 AC: 5774 AN: 36860

South Asian (SAS) AF: 0.322 AC: 25541 AN: 79232

European-Finnish (FIN) AF: 0.316 AC: 15761 AN: 49826

Middle Eastern (MID) AF: 0.295 AC: 1537 AN: 5206

European-Non Finnish (NFE) AF: 0.344 AC: 318047 AN: 924802

Other (OTH) AF: 0.311 AC: 16492 AN: 52990

GnomAD4 genome AF: 0.259 AC: 39369 AN: 151956 Hom.: 6005 Cov.: 32 AF XY: 0.259 AC XY: 19260 AN XY: 74254

African (AFR) AF: 0.0965 AC: 3998 AN: 41438

American (AMR) AF: 0.282 AC: 4312 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 1058 AN: 3468

East Asian (EAS) AF: 0.172 AC: 889 AN: 5162

South Asian (SAS) AF: 0.316 AC: 1519 AN: 4814

European-Finnish (FIN) AF: 0.326 AC: 3446 AN: 10572

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.341 AC: 23156 AN: 67910

Other (OTH) AF: 0.257 AC: 543 AN: 2110

Alfa AF: 0.285 Hom.: 761

Bravo AF: 0.248

Asia WGS AF: 0.276 AC: 958 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	1.3
DANN	Benign	0.92
PhyloP100		-0.52
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs41309970; hg19: chr9-140344204; COSMIC: COSV55810962; COSMIC: COSV55810962;