9-137449138-G-A

Position:

• chr9-137449138-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001130969.3(NSMF):​c.*256C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00722 in 583,848 control chromosomes in the GnomAD database, including 137 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (103 hom., cov: 33)
  • Exomes 𝑓: 0.0029 (34 hom.)
• Consequence: NSMF NM_001130969.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.240

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 9-137449138-G-A is Benign according to our data. Variant chr9-137449138-G-A is described in ClinVar as [Benign]. Clinvar id is 1281455.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NSMF	NM_001130969.3	c.*256C>T		3_prime_UTR_variant	16/16	ENST00000371475.9	NP_001124441.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NSMF	ENST00000371475.9	c.*256C>T		3_prime_UTR_variant	16/16	1	NM_001130969.3	ENSP00000360530	A1

Frequencies

GnomAD3 genomes AF: 0.0195 AC: 2969 AN: 152188 Hom.: 102 Cov.: 33

Gnomad AFR AF: 0.0675

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00713

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.0172

GnomAD4 exome AF: 0.00286 AC: 1233 AN: 431542 Hom.: 34 Cov.: 0 AF XY: 0.00229 AC XY: 520 AN XY: 226928

Gnomad4 AFR exome AF: 0.0709

Gnomad4 AMR exome AF: 0.00651

Gnomad4 ASJ exome AF: 0.00105

Gnomad4 EAS exome AF: 0.0000669

Gnomad4 SAS exome AF: 0.000242

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000338

Gnomad4 OTH exome AF: 0.00556

GnomAD4 genome AF: 0.0196 AC: 2981 AN: 152306 Hom.: 103 Cov.: 33 AF XY: 0.0184 AC XY: 1369 AN XY: 74462

Gnomad4 AFR AF: 0.0676

Gnomad4 AMR AF: 0.00712

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000353

Gnomad4 OTH AF: 0.0170

Alfa AF: 0.0123 Hom.: 11

Bravo AF: 0.0224

Asia WGS AF: 0.00462 AC: 16 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	May 14, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	11
DANN	Benign	0.92
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Other links and lift over

dbSNP: rs116710329; hg19: chr9-140343590;