rs61744333

Variant names:

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_001113491.2(SEPTIN9):c.201C>T(p.Gly67Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00281 in 1,613,790 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0029 ( 4 hom. )

Consequence

SEPTIN9
NM_001113491.2 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -1.50

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BP6

Variant 17-77402183-C-T is Benign according to our data. Variant chr17-77402183-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 325539.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-77402183-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.5 with no splicing effect.

BS2

High AC in GnomAd4 at 326 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEPTIN9	NM_001113491.2 link	c.201C>T	p.Gly67Gly	synonymous_variant	Exon 3 of 12	ENST00000427177.6	NP_001106963.1	Q9UHD8-1
SEPTIN9	NM_006640.5 link	c.147C>T	p.Gly49Gly	synonymous_variant	Exon 2 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.201C>T	p.Gly67Gly	synonymous_variant	Exon 3 of 12	1	NM_001113491.2	ENSP00000391249.1		Q9UHD8-1
SEPTIN9	ENST00000329047.13 link	c.147C>T	p.Gly49Gly	synonymous_variant	Exon 2 of 11	1	NM_006640.5	ENSP00000329161.8		Q9UHD8-2

Frequencies

GnomAD3 genomes

AF:

0.00214

AC:

325

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00255

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00337

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00202

AC:

503

AN:

248798

Hom.:

AF XY:

0.00210

AC XY:

284

AN XY:

135112

show subpopulations

Gnomad AFR exome

AF:

0.000972

Gnomad AMR exome

AF:

0.00203

Gnomad ASJ exome

AF:

0.00189

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.00134

Gnomad FIN exome

AF:

0.0000930

Gnomad NFE exome

AF:

0.00302

Gnomad OTH exome

AF:

0.00231

GnomAD4 exome

AF:

0.00288

AC:

4213

AN:

1461550

Hom.:

Cov.:

AF XY:

0.00290

AC XY:

2111

AN XY:

727060

show subpopulations

Gnomad4 AFR exome

AF:

0.000687

Gnomad4 AMR exome

AF:

0.00224

Gnomad4 ASJ exome

AF:

0.00172

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.00139

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.00336

Gnomad4 OTH exome

AF:

0.00277

GnomAD4 genome

AF:

0.00214

AC:

326

AN:

152240

Hom.:

Cov.:

AF XY:

0.00206

AC XY:

153

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.000963

Gnomad4 AMR

AF:

0.00255

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00337

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00261

Hom.:

Bravo

AF:

0.00226

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00322

EpiControl

AF:

0.00385

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SEPTIN9: BP4, BP7 -

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 05, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:2

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Dec 20, 2016

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Amyotrophic neuralgia

Benign:2

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. -

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

5.6

DANN

Benign

0.70

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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