dbSNP rs116710329: NSMF:c.*256C>T (chr9-137449138-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.240

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 -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130969.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NSMF	NM_001130969.3	MANE Select	c.*256C>T	3_prime_UTR	Exon 16 of 16	NP_001124441.1	Q6X4W1-1
NSMF	NM_015537.5		c.*256C>T	3_prime_UTR	Exon 15 of 15	NP_056352.3
NSMF	NM_001130970.2		c.*256C>T	3_prime_UTR	Exon 15 of 15	NP_001124442.1	Q6X4W1-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NSMF	ENST00000371475.9	TSL:1 MANE Select	c.*256C>T	3_prime_UTR	Exon 16 of 16	ENSP00000360530.3	Q6X4W1-1
NSMF	ENST00000265663.12	TSL:1	c.*256C>T	3_prime_UTR	Exon 15 of 15	ENSP00000265663.7	Q6X4W1-2
NSMF	ENST00000371474.7	TSL:1	c.*256C>T	3_prime_UTR	Exon 14 of 14	ENSP00000360529.3	Q6X4W1-6

Frequencies

GnomAD3 genomes

AF:

0.0195

AC:

2969

AN:

152188

Hom.:

102

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.00229

AC XY:

520

AN XY:

226928

show subpopulations

African (AFR)

AF:

0.0709

AC:

853

AN:

12032

American (AMR)

AF:

0.00651

AC:

118

AN:

18126

Ashkenazi Jewish (ASJ)

AF:

0.00105

AC:

AN:

13288

East Asian (EAS)

AF:

0.0000669

AC:

AN:

29882

South Asian (SAS)

AF:

0.000242

AC:

AN:

45548

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28146

Middle Eastern (MID)

AF:

0.00478

AC:

AN:

1884

European-Non Finnish (NFE)

AF:

0.000338

AC:

AN:

257644

Other (OTH)

AF:

0.00556

AC:

139

AN:

24992

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

119

178

238

297

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.0196

AC:

2981

AN:

152306

Hom.:

103

Cov.:

AF XY:

0.0184

AC XY:

1369

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.0676

AC:

2807

AN:

41540

American (AMR)

AF:

0.00712

AC:

109

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.000621

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000353

AC:

AN:

68016

Other (OTH)

AF:

0.0170

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

140

279

419

558

698

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<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:

0.0134

Hom.:

Bravo

AF:

0.0224

Asia WGS

AF:

0.00462

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

(source)

DANN

Benign

0.92

PhyloP100

-0.24

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over