17-77402416-C-T

Position:

chr17-77402416-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001113491.2(SEPTIN9):c.434C>T(p.Pro145Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 1,610,262 control chromosomes in the GnomAD database, including 9,038 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.081 ( 654 hom., cov: 32)

Exomes 𝑓: 0.10 ( 8384 hom. )

Consequence

SEPTIN9
NM_001113491.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.80

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017449558).

BP6

Variant 17-77402416-C-T is Benign according to our data. Variant chr17-77402416-C-T is described in ClinVar as [Benign]. Clinvar id is 325543.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-77402416-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEPTIN9	NM_001113491.2 linkuse as main transcript	c.434C>T	p.Pro145Leu	missense_variant	3/12	ENST00000427177.6	NP_001106963.1
SEPTIN9	NM_006640.5 linkuse as main transcript	c.380C>T	p.Pro127Leu	missense_variant	2/11	ENST00000329047.13	NP_006631.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEPTIN9	ENST00000427177.6 linkuse as main transcript	c.434C>T	p.Pro145Leu	missense_variant	3/12	1	NM_001113491.2	ENSP00000391249	A1	Q9UHD8-1
SEPTIN9	ENST00000329047.13 linkuse as main transcript	c.380C>T	p.Pro127Leu	missense_variant	2/11	1	NM_006640.5	ENSP00000329161	P3	Q9UHD8-2

Frequencies

GnomAD3 genomes

AF:

0.0810

AC:

12326

AN:

152148

Hom.:

655

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0215

Gnomad AMI

AF:

0.276

Gnomad AMR

AF:

0.107

Gnomad ASJ

AF:

0.0870

Gnomad EAS

AF:

0.0137

Gnomad SAS

AF:

0.0685

Gnomad FIN

AF:

0.0620

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.116

Gnomad OTH

AF:

0.105

GnomAD3 exomes

AF:

0.0834

AC:

19985

AN:

239538

Hom.:

995

AF XY:

0.0857

AC XY:

11236

AN XY:

131096

show subpopulations

Gnomad AFR exome

AF:

0.0177

Gnomad AMR exome

AF:

0.0707

Gnomad ASJ exome

AF:

0.0806

Gnomad EAS exome

AF:

0.00472

Gnomad SAS exome

AF:

0.0671

Gnomad FIN exome

AF:

0.0668

Gnomad NFE exome

AF:

0.116

Gnomad OTH exome

AF:

0.109

GnomAD4 exome

AF:

0.103

AC:

149545

AN:

1457996

Hom.:

8384

Cov.:

AF XY:

0.103

AC XY:

74348

AN XY:

725068

show subpopulations

Gnomad4 AFR exome

AF:

0.0197

Gnomad4 AMR exome

AF:

0.0725

Gnomad4 ASJ exome

AF:

0.0804

Gnomad4 EAS exome

AF:

0.0263

Gnomad4 SAS exome

AF:

0.0689

Gnomad4 FIN exome

AF:

0.0683

Gnomad4 NFE exome

AF:

0.114

Gnomad4 OTH exome

AF:

0.0990

GnomAD4 genome

AF:

0.0810

AC:

12329

AN:

152266

Hom.:

654

Cov.:

AF XY:

0.0791

AC XY:

5890

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0214

Gnomad4 AMR

AF:

0.107

Gnomad4 ASJ

AF:

0.0870

Gnomad4 EAS

AF:

0.0137

Gnomad4 SAS

AF:

0.0675

Gnomad4 FIN

AF:

0.0620

Gnomad4 NFE

AF:

0.116

Gnomad4 OTH

AF:

0.109

Alfa

AF:

0.101

Hom.:

421

Bravo

AF:

0.0813

TwinsUK

AF:

0.112

AC:

416

ALSPAC

AF:

0.111

AC:

429

ESP6500AA

AF:

0.0231

AC:

100

ESP6500EA

AF:

0.112

AC:

953

ExAC

AF:

0.0811

AC:

9811

Asia WGS

AF:

0.0480

AC:

168

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 21, 2018	- -

Amyotrophic neuralgia

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Jul 12, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.051

T;.;.;.;.;.;T

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.67

LIST_S2

Uncertain

0.92

D;D;D;.;D;D;D

MetaRNN

Benign

0.0017

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.5

M;.;.;.;.;.;.

MutationTaster

Benign

0.000042

P;P;P;P;P;P;P;P;P;P

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.6

N;.;N;.;.;N;.

REVEL

Benign

0.060

Sift

Uncertain

0.0030

D;.;D;.;.;D;.

Sift4G

Uncertain

0.037

D;T;T;T;D;D;D

Polyphen

0.86

P;B;D;D;.;P;.

Vest4

0.18

MPC

0.15

ClinPred

0.025

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.060

gMVP

0.13

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