9-137459023-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2

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

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.456

Publications

0 publications found

Variant links:

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

NSMF links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 CliVar as Benign/Likely_benign. Clinvar id is 138563.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-137459023-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 138563.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-137459023-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 138563.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-137459023-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 138563.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-137459023-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 138563.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-137459023-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 138563.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-137459023-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 138563.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-137459023-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 138563.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-137459023-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 138563.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-137459023-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 138563.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-137459023-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 138563.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-137459023-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 138563.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-137459023-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 138563.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-137459023-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 138563.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-137459023-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 138563.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-137459023-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 138563.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-137459023-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 138563.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-137459023-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 138563.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-137459023-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 138563.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-137459023-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 138563.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-137459023-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 138563.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-137459023-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 138563.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-137459023-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 138563.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-137459023-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 138563.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-137459023-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 138563.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-137459023-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 138563.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-137459023-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 138563.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 190 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NSMF	NM_001130969.3 link	c.71+9G>A		intron_variant	Intron 1 of 15	ENST00000371475.9	NP_001124441.1	Q6X4W1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NSMF	ENST00000371475.9 link	c.71+9G>A		intron_variant	Intron 1 of 15	1	NM_001130969.3	ENSP00000360530.3		Q6X4W1-1
NSMF	ENST00000371472.6 link	c.71+9G>A		intron_variant	Intron 1 of 15	2		ENSP00000360527.1		Q6X4W1-2

Frequencies

GnomAD3 genomes

AF:

0.00125

AC:

190

AN:

151918

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.00221

AC:

AN:

7698

AF XY:

0.00108

show subpopulations

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 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.:

Cov.:

AF XY:

0.00289

AC XY:

1561

AN XY:

539712

show subpopulations

African (AFR)

AF:

0.000438

AC:

AN:

22806

American (AMR)

AF:

0.000730

AC:

AN:

9586

Ashkenazi Jewish (ASJ)

AF:

0.0000649

AC:

AN:

15410

East Asian (EAS)

AF:

0.00

AC:

AN:

25884

South Asian (SAS)

AF:

0.00

AC:

AN:

34294

European-Finnish (FIN)

AF:

0.000285

AC:

AN:

24530

Middle Eastern (MID)

AF:

0.000326

AC:

AN:

3070

European-Non Finnish (NFE)

AF:

0.00334

AC:

3167

AN:

947152

Other (OTH)

AF:

0.00302

AC:

138

AN:

45688

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

144

287

431

574

718

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

142

284

426

568

710

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00125

AC:

190

AN:

152026

Hom.:

Cov.:

AF XY:

0.00109

AC XY:

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.000458

AC:

AN:

41518

American (AMR)

AF:

0.000654

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.000379

AC:

AN:

10552

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00230

AC:

156

AN:

67896

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00122

Hom.:

Bravo

AF:

0.00134

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Mar 18, 2025

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 04, 2013

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Dec 09, 2016

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Jul 27, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

6.8

(source)

DANN

Benign

0.97

PhyloP100

-0.46

PromoterAI

-0.0022

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over