Variant 9-137449558-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001130969.3(NSMF):c.1495+41G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0389 in 1,610,752 control chromosomes in the GnomAD database, including 3,236 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.087 ( 1178 hom., cov: 33)

Exomes 𝑓: 0.034 ( 2058 hom. )

Consequence

NSMF
NM_001130969.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.216

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 9-137449558-C-T is Benign according to our data. Variant chr9-137449558-C-T is described in ClinVar as [Benign]. Clinvar id is 673559.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NSMF	NM_001130969.3 linkuse as main transcript	c.1495+41G>A		intron_variant		ENST00000371475.9	NP_001124441.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NSMF	ENST00000371475.9 linkuse as main transcript	c.1495+41G>A		intron_variant		1	NM_001130969.3	ENSP00000360530	A1	Q6X4W1-1

Frequencies

GnomAD3 genomes

AF:

0.0866

AC:

13181

AN:

152136

Hom.:

1173

Cov.:

show subpopulations

Gnomad AFR

AF:

0.220

Gnomad AMI

AF:

0.0186

Gnomad AMR

AF:

0.0398

Gnomad ASJ

AF:

0.0179

Gnomad EAS

AF:

0.170

Gnomad SAS

AF:

0.0863

Gnomad FIN

AF:

0.0352

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0227

Gnomad OTH

AF:

0.0736

GnomAD3 exomes

AF:

0.0542

AC:

13404

AN:

247406

Hom.:

850

AF XY:

0.0519

AC XY:

6969

AN XY:

134382

show subpopulations

Gnomad AFR exome

AF:

0.228

Gnomad AMR exome

AF:

0.0278

Gnomad ASJ exome

AF:

0.0171

Gnomad EAS exome

AF:

0.164

Gnomad SAS exome

AF:

0.0746

Gnomad FIN exome

AF:

0.0343

Gnomad NFE exome

AF:

0.0218

Gnomad OTH exome

AF:

0.0426

GnomAD4 exome

AF:

0.0339

AC:

49503

AN:

1458498

Hom.:

2058

Cov.:

AF XY:

0.0346

AC XY:

25129

AN XY:

725598

show subpopulations

Gnomad4 AFR exome

AF:

0.220

Gnomad4 AMR exome

AF:

0.0282

Gnomad4 ASJ exome

AF:

0.0159

Gnomad4 EAS exome

AF:

0.163

Gnomad4 SAS exome

AF:

0.0720

Gnomad4 FIN exome

AF:

0.0357

Gnomad4 NFE exome

AF:

0.0207

Gnomad4 OTH exome

AF:

0.0465

GnomAD4 genome

AF:

0.0867

AC:

13208

AN:

152254

Hom.:

1178

Cov.:

AF XY:

0.0868

AC XY:

6461

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.220

Gnomad4 AMR

AF:

0.0398

Gnomad4 ASJ

AF:

0.0179

Gnomad4 EAS

AF:

0.170

Gnomad4 SAS

AF:

0.0859

Gnomad4 FIN

AF:

0.0352

Gnomad4 NFE

AF:

0.0227

Gnomad4 OTH

AF:

0.0757

Alfa

AF:

0.0245

Hom.:

Bravo

AF:

0.0918

Asia WGS

AF:

0.107

AC:

369

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2018	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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.2

DANN

Benign

0.58

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over