17-77317253-A-G

Variant names:

• chr17-77317253-A-G
• rs4788985
• NM_001113491.2:c.76+10056A>G

Variant summary

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

The NM_001113491.2(SEPTIN9):​c.76+10056A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 151,920 control chromosomes in the GnomAD database, including 14,002 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 (14002 hom., cov: 31)
• Consequence: SEPTIN9 NM_001113491.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0480
• Publications: 14 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: PanelApp Australia, 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.514 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEPTIN9	NM_001113491.2	MANE Select	c.76+10056A>G		intron	N/A	NP_001106963.1	Q9UHD8-1
	SEPTIN9	NM_001293695.2		c.19+35699A>G		intron	N/A	NP_001280624.1	Q9UHD8-7
	SEPTIN9	NM_001113492.2		c.-417+10056A>G		intron	N/A	NP_001106964.1	Q9UHD8-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEPTIN9	ENST00000427177.6	TSL:1 MANE Select	c.76+10056A>G		intron	N/A	ENSP00000391249.1	Q9UHD8-1
	SEPTIN9	ENST00000873888.1		c.76+10056A>G		intron	N/A	ENSP00000543947.1
	SEPTIN9	ENST00000873887.1		c.76+10056A>G		intron	N/A	ENSP00000543946.1

Frequencies

GnomAD3 genomes AF: 0.408 AC: 61901 AN: 151802 Hom.: 14005 Cov.: 31

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.548

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.408

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

GnomAD4 genome AF: 0.408 AC: 61913 AN: 151920 Hom.: 14002 Cov.: 31 AF XY: 0.413 AC XY: 30673 AN XY: 74234

African (AFR) AF: 0.196 AC: 8114 AN: 41464

American (AMR) AF: 0.500 AC: 7637 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.451 AC: 1563 AN: 3468

East Asian (EAS) AF: 0.531 AC: 2730 AN: 5144

South Asian (SAS) AF: 0.487 AC: 2344 AN: 4812

European-Finnish (FIN) AF: 0.517 AC: 5442 AN: 10534

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.480 AC: 32575 AN: 67918

Other (OTH) AF: 0.411 AC: 863 AN: 2102

Alfa AF: 0.462 Hom.: 70294

Bravo AF: 0.396

Asia WGS AF: 0.452 AC: 1568 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.7
DANN	Benign	0.54
PhyloP100		0.048
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: rs4788985; hg19: chr17-75313335;