chr17-77404018-T-A

Variant names:

• chr17-77404018-T-A
• rs892961
• NM_001113491.2:c.721+1315T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001113491.2(SEPTIN9):​c.721+1315T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 151,958 control chromosomes in the GnomAD database, including 13,532 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.41 (13532 hom., cov: 32)
• Consequence: SEPTIN9 NM_001113491.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31
• Publications: 16 publications found

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: Labcorp Genetics (formerly Invitae)
• neuralgic amyotrophy

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEPTIN9	NM_001113491.2	MANE Select	c.721+1315T>A		intron	N/A	NP_001106963.1
	SEPTIN9	NM_006640.5	MANE Plus Clinical	c.667+1315T>A		intron	N/A	NP_006631.2
	SEPTIN9	NM_001113493.2		c.700+1315T>A		intron	N/A	NP_001106965.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEPTIN9	ENST00000427177.6	TSL:1 MANE Select	c.721+1315T>A		intron	N/A	ENSP00000391249.1
	SEPTIN9	ENST00000329047.13	TSL:1 MANE Plus Clinical	c.667+1315T>A		intron	N/A	ENSP00000329161.8
	SEPTIN9	ENST00000423034.6	TSL:1	c.700+1315T>A		intron	N/A	ENSP00000405877.1

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62745 AN: 151840 Hom.: 13506 Cov.: 32

Gnomad AFR AF: 0.514

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.412

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

GnomAD4 genome AF: 0.413 AC: 62813 AN: 151958 Hom.: 13532 Cov.: 32 AF XY: 0.405 AC XY: 30085 AN XY: 74256

African (AFR) AF: 0.514 AC: 21300 AN: 41422

American (AMR) AF: 0.308 AC: 4696 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 1404 AN: 3468

East Asian (EAS) AF: 0.199 AC: 1030 AN: 5176

South Asian (SAS) AF: 0.320 AC: 1547 AN: 4828

European-Finnish (FIN) AF: 0.371 AC: 3914 AN: 10542

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.408 AC: 27709 AN: 67952

Other (OTH) AF: 0.411 AC: 868 AN: 2110

Alfa AF: 0.412 Hom.: 1660

Bravo AF: 0.413

Asia WGS AF: 0.291 AC: 1014 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.18
DANN	Benign	0.73
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs892961; hg19: chr17-75400100;