rs61744333

Variant names:

• chr17-77402183-C-T
• rs61744333
• NM_001113491.2:c.201C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -1.50
• Publications: 1 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 325539.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.5 with no splicing effect.
• BS2: High AC in GnomAd4 at 326 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001113491.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEPTIN9	NM_001113491.2	MANE Select	c.201C>T	p.Gly67Gly	synonymous	Exon 3 of 12	NP_001106963.1
	SEPTIN9	NM_006640.5	MANE Plus Clinical	c.147C>T	p.Gly49Gly	synonymous	Exon 2 of 11	NP_006631.2
	SEPTIN9	NM_001113493.2		c.180C>T	p.Gly60Gly	synonymous	Exon 2 of 11	NP_001106965.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEPTIN9	ENST00000427177.6	TSL:1 MANE Select	c.201C>T	p.Gly67Gly	synonymous	Exon 3 of 12	ENSP00000391249.1
	SEPTIN9	ENST00000329047.13	TSL:1 MANE Plus Clinical	c.147C>T	p.Gly49Gly	synonymous	Exon 2 of 11	ENSP00000329161.8
	SEPTIN9	ENST00000423034.6	TSL:1	c.180C>T	p.Gly60Gly	synonymous	Exon 2 of 11	ENSP00000405877.1

Frequencies

GnomAD3 genomes AF: 0.00214 AC: 325 AN: 152122 Hom.: 0 Cov.: 32

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

GnomAD2 exomes AF: 0.00202 AC: 503 AN: 248798 AF XY: 0.00210

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 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.: 4 Cov.: 32 AF XY: 0.00290 AC XY: 2111 AN XY: 727060

African (AFR) AF: 0.000687 AC: 23 AN: 33480

American (AMR) AF: 0.00224 AC: 100 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00172 AC: 45 AN: 26136

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39700

South Asian (SAS) AF: 0.00139 AC: 120 AN: 86258

European-Finnish (FIN) AF: 0.000131 AC: 7 AN: 53248

Middle Eastern (MID) AF: 0.00260 AC: 15 AN: 5768

European-Non Finnish (NFE) AF: 0.00336 AC: 3731 AN: 1111868

Other (OTH) AF: 0.00277 AC: 167 AN: 60370

GnomAD4 genome AF: 0.00214 AC: 326 AN: 152240 Hom.: 0 Cov.: 32 AF XY: 0.00206 AC XY: 153 AN XY: 74432

African (AFR) AF: 0.000963 AC: 40 AN: 41546

American (AMR) AF: 0.00255 AC: 39 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5170

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00337 AC: 229 AN: 68004

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.00261 Hom.: 0

Bravo AF: 0.00226

Asia WGS AF: 0.000289 AC: 1 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

Submissions by phenotype

not provided Benign:5

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Jan 05, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

not specified Benign:2

Dec 20, 2016

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	5.6
DANN	Benign	0.70
PhyloP100		-1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=294/6	polymorphism

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

Other links and lift over

dbSNP: rs61744333; hg19: chr17-75398265; COSMIC: COSV61203236; COSMIC: COSV61203236;