Genetic Variant SEPTIN9:c.20-121G>A (chr17-77307020-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_001113491.2(SEPTIN9):c.20-121G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0496 in 976,054 control chromosomes in the GnomAD database, including 1,561 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.066 ( 485 hom., cov: 33)

Exomes 𝑓: 0.047 ( 1076 hom. )

Consequence

SEPTIN9
NM_001113491.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.880

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 (BayesDel_noAF=-0.88).

BP6

Variant 17-77307020-G-A is Benign according to our data. Variant chr17-77307020-G-A is described in ClinVar as [Benign]. Clinvar id is 1230464.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-77307020-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SEPTIN9	NM_001113491.2 link	c.20-121G>A	intron_variant	Intron 1 of 11	ENST00000427177.6	NP_001106963.1	Q9UHD8-1
SEPTIN9	NM_001293695.2 link	c.19+25466G>A	intron_variant	Intron 1 of 10		NP_001280624.1	Q9UHD8-7
SEPTIN9	NM_001113492.2 link	c.-473-121G>A	intron_variant	Intron 1 of 11		NP_001106964.1	Q9UHD8-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEPTIN9	ENST00000427177.6 link	c.20-121G>A		intron_variant	Intron 1 of 11	1	NM_001113491.2	ENSP00000391249.1		Q9UHD8-1

Frequencies

GnomAD3 genomes

AF:

0.0658

AC:

10018

AN:

152156

Hom.:

486

Cov.:

show subpopulations

Gnomad AFR

AF:

0.124

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.0497

Gnomad ASJ

AF:

0.0366

Gnomad EAS

AF:

0.0564

Gnomad SAS

AF:

0.0427

Gnomad FIN

AF:

0.00970

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0476

Gnomad OTH

AF:

0.0592

GnomAD4 exome

AF:

0.0466

AC:

38416

AN:

823780

Hom.:

1076

AF XY:

0.0462

AC XY:

20086

AN XY:

434398

show subpopulations

Gnomad4 AFR exome

AF:

0.120

Gnomad4 AMR exome

AF:

0.0313

Gnomad4 ASJ exome

AF:

0.0346

Gnomad4 EAS exome

AF:

0.0584

Gnomad4 SAS exome

AF:

0.0424

Gnomad4 FIN exome

AF:

0.0121

Gnomad4 NFE exome

AF:

0.0483

Gnomad4 OTH exome

AF:

0.0496

GnomAD4 genome

AF:

0.0659

AC:

10034

AN:

152274

Hom.:

485

Cov.:

AF XY:

0.0645

AC XY:

4806

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.124

Gnomad4 AMR

AF:

0.0496

Gnomad4 ASJ

AF:

0.0366

Gnomad4 EAS

AF:

0.0565

Gnomad4 SAS

AF:

0.0435

Gnomad4 FIN

AF:

0.00970

Gnomad4 NFE

AF:

0.0476

Gnomad4 OTH

AF:

0.0581

Alfa

AF:

0.0531

Hom.:

Bravo

AF:

0.0706

Asia WGS

AF:

0.0450

AC:

159

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 17, 2018

GeneDx

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.0

DANN

Benign

0.52

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