17-77402298-C-A

Variant names:

• chr17-77402298-C-A
• rs80338761
• NM_001113491.2:c.316C>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001113491.2(SEPTIN9):​c.316C>A​(p.Arg106Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,356 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SEPTIN9 NM_001113491.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23
• Publications: 0 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BP7: Synonymous conserved (PhyloP=1.23 with no splicing effect.

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.316C>A	p.Arg106Arg	synonymous	Exon 3 of 12	NP_001106963.1	Q9UHD8-1
	SEPTIN9	NM_006640.5	MANE Plus Clinical	c.262C>A	p.Arg88Arg	synonymous	Exon 2 of 11	NP_006631.2	Q9UHD8-2
	SEPTIN9	NM_001113493.2		c.295C>A	p.Arg99Arg	synonymous	Exon 2 of 11	NP_001106965.1	Q9UHD8-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEPTIN9	ENST00000427177.6	TSL:1 MANE Select	c.316C>A	p.Arg106Arg	synonymous	Exon 3 of 12	ENSP00000391249.1	Q9UHD8-1
	SEPTIN9	ENST00000329047.13	TSL:1 MANE Plus Clinical	c.262C>A	p.Arg88Arg	synonymous	Exon 2 of 11	ENSP00000329161.8	Q9UHD8-2
	SEPTIN9	ENST00000423034.6	TSL:1	c.295C>A	p.Arg99Arg	synonymous	Exon 2 of 11	ENSP00000405877.1	Q9UHD8-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460356 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726540

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26098

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52310

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111768

Other (OTH) AF: 0.00 AC: 0 AN: 60340

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	12
DANN	Benign	0.59
PhyloP100		1.2

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: rs80338761; hg19: chr17-75398380;