Variant 9-137449752-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 ENST00000371475.9(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
ENST00000371475.9 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.519

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=-0.73).

BP6

Variant 9-137449752-C-T is Benign according to our data. Variant chr9-137449752-C-T is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NSMF	NM_001130969.3 linkuse as main transcript	c.1420-78G>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.1420-78G>A		intron_variant		1	NM_001130969.3	ENSP00000360530	A1	Q6X4W1-1

Frequencies

GnomAD3 genomes

AF:

0.259

AC:

39378

AN:

151838

Hom.:

6004

Cov.:

show subpopulations

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.:

AF XY:

0.327

AC XY:

203939

AN XY:

623750

show subpopulations

Gnomad4 AFR exome

AF:

0.0865

Gnomad4 AMR exome

AF:

0.291

Gnomad4 ASJ exome

AF:

0.301

Gnomad4 EAS exome

AF:

0.157

Gnomad4 SAS exome

AF:

0.322

Gnomad4 FIN exome

AF:

0.316

Gnomad4 NFE exome

AF:

0.344

Gnomad4 OTH exome

AF:

0.311

GnomAD4 genome

AF:

0.259

AC:

39369

AN:

151956

Hom.:

6005

Cov.:

AF XY:

0.259

AC XY:

19260

AN XY:

74254

show subpopulations

Gnomad4 AFR

AF:

0.0965

Gnomad4 AMR

AF:

0.282

Gnomad4 ASJ

AF:

0.305

Gnomad4 EAS

AF:

0.172

Gnomad4 SAS

AF:

0.316

Gnomad4 FIN

AF:

0.326

Gnomad4 NFE

AF:

0.341

Gnomad4 OTH

AF:

0.257

Alfa

AF:

0.285

Hom.:

761

Bravo

AF:

0.248

Asia WGS

AF:

0.276

AC:

958

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

-0.73

CADD

Benign

1.3

DANN

Benign

0.92

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