Genetic Variant SEPTIN9:c.76+236G>C (chr17-77307433-G-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001113491.2(SEPTIN9):c.76+236G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00402 in 152,330 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0040 ( 10 hom., cov: 32)

Consequence

SEPTIN9
NM_001113491.2 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.44

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

amyotrophic neuralgia
Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
neuralgic amyotrophy
Inheritance: AD Classification: MODERATE Submitted by: ClinGen

SEPTIN9 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 17-77307433-G-C is Benign according to our data. Variant chr17-77307433-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1189788.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 613 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SEPTIN9	NM_001113491.2	MANE Select	c.76+236G>C	intron	N/A	NP_001106963.1	Q9UHD8-1
SEPTIN9	NM_001293695.2		c.19+25879G>C	intron	N/A	NP_001280624.1	Q9UHD8-7
SEPTIN9	NM_001113492.2		c.-417+236G>C	intron	N/A	NP_001106964.1	Q9UHD8-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SEPTIN9	ENST00000427177.6	TSL:1 MANE Select	c.76+236G>C	intron	N/A	ENSP00000391249.1	Q9UHD8-1
SEPTIN9	ENST00000873888.1		c.76+236G>C	intron	N/A	ENSP00000543947.1
SEPTIN9	ENST00000873887.1		c.76+236G>C	intron	N/A	ENSP00000543946.1

Frequencies

GnomAD3 genomes

AF:

0.00403

AC:

613

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0141

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00334

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.00402

AC:

613

AN:

152330

Hom.:

Cov.:

AF XY:

0.00395

AC XY:

294

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.0140

AC:

583

AN:

41566

American (AMR)

AF:

0.00118

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68032

Other (OTH)

AF:

0.00331

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

122

153

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00243

Hom.:

Bravo

AF:

0.00469

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

7.9

(source)

DANN

Benign

0.75

PhyloP100

1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over