Variant chr17-77281529-A-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001113491.2(SEPTIN9):c.-7A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0929 in 1,548,048 control chromosomes in the GnomAD database, including 9,435 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2799 hom., cov: 33)

Exomes 𝑓: 0.087 ( 6636 hom. )

Consequence

SEPTIN9
NM_001113491.2 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.353

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:

SEPTIN9-DT (HGNC:52818): (SEPTIN9 divergent transcript)

SEPTIN9-DT links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 17-77281529-A-C is Benign according to our data. Variant chr17-77281529-A-C is described in ClinVar as [Benign]. Clinvar id is 1239714.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-77281529-A-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein	UniProt
SEPTIN9	NM_001113491.2 link	c.-7A>C	5_prime_UTR_variant	1/12	ENST00000427177.6	NP_001106963.1	Q9UHD8-1
SEPTIN9	NM_001293695.2 link	c.-7A>C	5_prime_UTR_variant	1/11		NP_001280624.1	Q9UHD8-7
SEPTIN9-DT	NR_136503.1 link	n.286+83T>G	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEPTIN9	ENST00000427177 link	c.-7A>C		5_prime_UTR_variant	1/12	1	NM_001113491.2	ENSP00000391249.1		Q9UHD8-1

Frequencies

GnomAD3 genomes

AF:

0.151

AC:

22901

AN:

151948

Hom.:

2790

Cov.:

show subpopulations

Gnomad AFR

AF:

0.339

Gnomad AMI

AF:

0.0934

Gnomad AMR

AF:

0.0883

Gnomad ASJ

AF:

0.0743

Gnomad EAS

AF:

0.0869

Gnomad SAS

AF:

0.128

Gnomad FIN

AF:

0.0373

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0795

Gnomad OTH

AF:

0.148

GnomAD3 exomes

AF:

0.0871

AC:

12898

AN:

148096

Hom.:

852

AF XY:

0.0887

AC XY:

7092

AN XY:

79990

show subpopulations

Gnomad AFR exome

AF:

0.322

Gnomad AMR exome

AF:

0.0547

Gnomad ASJ exome

AF:

0.0713

Gnomad EAS exome

AF:

0.0849

Gnomad SAS exome

AF:

0.124

Gnomad FIN exome

AF:

0.0413

Gnomad NFE exome

AF:

0.0766

Gnomad OTH exome

AF:

0.0814

GnomAD4 exome

AF:

0.0866

AC:

120909

AN:

1395986

Hom.:

6636

Cov.:

AF XY:

0.0869

AC XY:

59856

AN XY:

688908

show subpopulations

Gnomad4 AFR exome

AF:

0.350

Gnomad4 AMR exome

AF:

0.0590

Gnomad4 ASJ exome

AF:

0.0704

Gnomad4 EAS exome

AF:

0.0715

Gnomad4 SAS exome

AF:

0.123

Gnomad4 FIN exome

AF:

0.0442

Gnomad4 NFE exome

AF:

0.0794

Gnomad4 OTH exome

AF:

0.0996

GnomAD4 genome

AF:

0.151

AC:

22946

AN:

152062

Hom.:

2799

Cov.:

AF XY:

0.148

AC XY:

10992

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.339

Gnomad4 AMR

AF:

0.0881

Gnomad4 ASJ

AF:

0.0743

Gnomad4 EAS

AF:

0.0872

Gnomad4 SAS

AF:

0.129

Gnomad4 FIN

AF:

0.0373

Gnomad4 NFE

AF:

0.0796

Gnomad4 OTH

AF:

0.146

Alfa

AF:

0.0906

Hom.:

445

Bravo

AF:

0.162

Asia WGS

AF:

0.114

AC:

397

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 06, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

SEPTIN9-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 28, 2019

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

-0.63

CADD

Benign

DANN

Benign

0.83

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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