rs3765043

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001113491.2(SEPTIN9):c.936C>T(p.Ser312Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00498 in 1,606,656 control chromosomes in the GnomAD database, including 193 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 34 hom., cov: 31)

Exomes 𝑓: 0.0043 ( 159 hom. )

Consequence

SEPTIN9
NM_001113491.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.670

Publications

3 publications found

Variant links:

Genes affected

SEPTIN9 (HGNC:7323): (septin 9) This gene is a member of the septin family involved in cytokinesis and cell cycle control. This gene is a candidate for the ovarian tumor suppressor gene. Mutations in this gene cause hereditary neuralgic amyotrophy, also known as neuritis with brachial predilection. A chromosomal translocation involving this gene on chromosome 17 and the MLL gene on chromosome 11 results in acute myelomonocytic leukemia. Multiple alternatively spliced transcript variants encoding different isoforms have been described.[provided by RefSeq, Mar 2009]

SEPTIN9 Gene-Disease associations (from GenCC):

amyotrophic neuralgia
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
neuralgic amyotrophy
Inheritance: AD Classification: MODERATE Submitted by: ClinGen

SEPTIN9 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.28).

BP6

Variant 17-77487446-C-T is Benign according to our data. Variant chr17-77487446-C-T is described in ClinVar as Benign. ClinVar VariationId is 325552.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEPTIN9	NM_001113491.2 link	c.936C>T	p.Ser312Ser	synonymous_variant	Exon 5 of 12	ENST00000427177.6	NP_001106963.1	Q9UHD8-1
SEPTIN9	NM_006640.5 link	c.882C>T	p.Ser294Ser	synonymous_variant	Exon 4 of 11	ENST00000329047.13	NP_006631.2	Q9UHD8-2A0A0S2Z5A5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEPTIN9	ENST00000427177.6 link	c.936C>T	p.Ser312Ser	synonymous_variant	Exon 5 of 12	1	NM_001113491.2	ENSP00000391249.1		Q9UHD8-1
SEPTIN9	ENST00000329047.13 link	c.882C>T	p.Ser294Ser	synonymous_variant	Exon 4 of 11	1	NM_006640.5	ENSP00000329161.8		Q9UHD8-2

Frequencies

GnomAD3 genomes

AF:

0.0110

AC:

1674

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0236

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00295

Gnomad ASJ

AF:

0.000866

Gnomad EAS

AF:

0.0782

Gnomad SAS

AF:

0.00766

Gnomad FIN

AF:

0.0121

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000941

Gnomad OTH

AF:

0.00717

GnomAD2 exomes

AF:

0.0102

AC:

2399

AN:

235848

AF XY:

0.00943

show subpopulations

Gnomad AFR exome

AF:

0.0255

Gnomad AMR exome

AF:

0.000760

Gnomad ASJ exome

AF:

0.00133

Gnomad EAS exome

AF:

0.0843

Gnomad FIN exome

AF:

0.0131

Gnomad NFE exome

AF:

0.00129

Gnomad OTH exome

AF:

0.00448

GnomAD4 exome

AF:

0.00434

AC:

6319

AN:

1454400

Hom.:

159

Cov.:

AF XY:

0.00432

AC XY:

3125

AN XY:

722904

show subpopulations

African (AFR)

AF:

0.0244

AC:

812

AN:

33298

American (AMR)

AF:

0.00108

AC:

AN:

43448

Ashkenazi Jewish (ASJ)

AF:

0.000886

AC:

AN:

25974

East Asian (EAS)

AF:

0.0844

AC:

3314

AN:

39264

South Asian (SAS)

AF:

0.00546

AC:

464

AN:

84942

European-Finnish (FIN)

AF:

0.0145

AC:

759

AN:

52504

Middle Eastern (MID)

AF:

0.00347

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.000475

AC:

527

AN:

1109096

Other (OTH)

AF:

0.00587

AC:

353

AN:

60114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

355

710

1066

1421

1776

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

180

270

360

450

<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:

0.0110

AC:

1679

AN:

152256

Hom.:

Cov.:

AF XY:

0.0119

AC XY:

883

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.0236

AC:

982

AN:

41554

American (AMR)

AF:

0.00294

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.000866

AC:

AN:

3466

East Asian (EAS)

AF:

0.0782

AC:

404

AN:

5166

South Asian (SAS)

AF:

0.00788

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0121

AC:

128

AN:

10618

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000941

AC:

AN:

68014

Other (OTH)

AF:

0.00662

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

161

242

322

403

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<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:

0.00429

Hom.:

Bravo

AF:

0.0120

Asia WGS

AF:

0.0330

AC:

113

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 27, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Amyotrophic neuralgia

Benign:2

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not specified

Benign:1

Apr 11, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

SEPTIN9-related disorder

Benign:1

Aug 08, 2024

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Benign

0.71

PhyloP100

0.67

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=74/26

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over