Variant chr9-137449876-G-A 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.1419+47C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 1,503,060 control chromosomes in the GnomAD database, including 35,683 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2919 hom., cov: 33)

Exomes 𝑓: 0.21 ( 32764 hom. )

Consequence

NSMF
NM_001130969.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.452

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 9-137449876-G-A is Benign according to our data. Variant chr9-137449876-G-A is described in ClinVar as [Benign]. Clinvar id is 1271348.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.457 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.1419+47C>T		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.1419+47C>T		intron_variant		1	NM_001130969.3	ENSP00000360530	A1	Q6X4W1-1

Frequencies

GnomAD3 genomes

AF:

0.170

AC:

25840

AN:

152080

Hom.:

2923

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0436

Gnomad AMI

AF:

0.207

Gnomad AMR

AF:

0.204

Gnomad ASJ

AF:

0.297

Gnomad EAS

AF:

0.472

Gnomad SAS

AF:

0.269

Gnomad FIN

AF:

0.142

Gnomad MID

AF:

0.282

Gnomad NFE

AF:

0.205

Gnomad OTH

AF:

0.216

GnomAD3 exomes

AF:

0.219

AC:

54429

AN:

248112

Hom.:

7054

AF XY:

0.225

AC XY:

30380

AN XY:

134962

show subpopulations

Gnomad AFR exome

AF:

0.0376

Gnomad AMR exome

AF:

0.171

Gnomad ASJ exome

AF:

0.313

Gnomad EAS exome

AF:

0.474

Gnomad SAS exome

AF:

0.254

Gnomad FIN exome

AF:

0.151

Gnomad NFE exome

AF:

0.212

Gnomad OTH exome

AF:

0.238

GnomAD4 exome

AF:

0.210

AC:

283876

AN:

1350862

Hom.:

32764

Cov.:

AF XY:

0.213

AC XY:

144101

AN XY:

677986

show subpopulations

Gnomad4 AFR exome

AF:

0.0363

Gnomad4 AMR exome

AF:

0.178

Gnomad4 ASJ exome

AF:

0.302

Gnomad4 EAS exome

AF:

0.478

Gnomad4 SAS exome

AF:

0.250

Gnomad4 FIN exome

AF:

0.151

Gnomad4 NFE exome

AF:

0.203

Gnomad4 OTH exome

AF:

0.220

GnomAD4 genome

AF:

0.170

AC:

25840

AN:

152198

Hom.:

2919

Cov.:

AF XY:

0.172

AC XY:

12800

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.0434

Gnomad4 AMR

AF:

0.204

Gnomad4 ASJ

AF:

0.297

Gnomad4 EAS

AF:

0.472

Gnomad4 SAS

AF:

0.269

Gnomad4 FIN

AF:

0.142

Gnomad4 NFE

AF:

0.205

Gnomad4 OTH

AF:

0.216

Alfa

AF:

0.210

Hom.:

3639

Bravo

AF:

0.173

Asia WGS

AF:

0.357

AC:

1242

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 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.4

DANN

Benign

0.41

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

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