17-77319217-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001113491.2(SEPTIN9):c.76+12020T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.892 in 152,214 control chromosomes in the GnomAD database, including 60,686 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.89 (60686 hom., cov: 32)
• Consequence: SEPTIN9 NM_001113491.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.52

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 17-77319217-T-C is Benign according to our data. Variant chr17-77319217-T-C is described in ClinVar as [Benign]. Clinvar id is 1220698.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEPTIN9	NM_001113491.2	c.76+12020T>C		intron_variant		ENST00000427177.6
SEPTIN9	NM_001113492.2	c.-417+12020T>C		intron_variant
SEPTIN9	NM_001293695.2	c.19+37663T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEPTIN9	ENST00000427177.6	c.76+12020T>C		intron_variant		1	NM_001113491.2	A1

Frequencies

GnomAD3 genomes AF: 0.892 AC: 135599 AN: 152096 Hom.: 60632 Cov.: 32

Gnomad AFR AF: 0.955

Gnomad AMI AF: 0.815

Gnomad AMR AF: 0.917

Gnomad ASJ AF: 0.904

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.939

Gnomad FIN AF: 0.859

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.841

Gnomad OTH AF: 0.893

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

GnomAD4 genome AF: 0.892 AC: 135709 AN: 152214 Hom.: 60686 Cov.: 32 AF XY: 0.895 AC XY: 66590 AN XY: 74404

Gnomad4 AFR AF: 0.955

Gnomad4 AMR AF: 0.917

Gnomad4 ASJ AF: 0.904

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.938

Gnomad4 FIN AF: 0.859

Gnomad4 NFE AF: 0.841

Gnomad4 OTH AF: 0.889

Alfa AF: 0.861 Hom.: 16565

Bravo AF: 0.899

Asia WGS AF: 0.959 AC: 3336 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.87
Dann	Benign	0.35

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

Other links and lift over

dbSNP: rs9889391; hg19: chr17-75315299;