rs80338760

Variant names:

• chr17-77320193-G-C
• rs80338760
• NM_006640.5:c.-134G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 3P and 1B. PM2 PP5 BP4

The NM_006640.5(SEPTIN9):​c.-134G>C variant causes a 5 prime UTR change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SEPTIN9 NM_006640.5 5_prime_UTR
• Clinical Significance: Pathogenic no assertion criteria provided P:1 O:1
• Conservation: PhyloP100: 7.19
• Publications: 3 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 17-77320193-G-C is Pathogenic according to our data. Variant chr17-77320193-G-C is described in ClinVar as Pathogenic. ClinVar VariationId is 5865.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38). . Strength limited to SUPPORTING due to the PP5.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006640.5. 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_006640.5	MANE Plus Clinical	c.-134G>C		5_prime_UTR	Exon 1 of 11	NP_006631.2	Q9UHD8-2
	SEPTIN9	NM_001113491.2	MANE Select	c.76+12996G>C		intron	N/A	NP_001106963.1	Q9UHD8-1
	SEPTIN9	NM_001293695.2		c.19+38639G>C		intron	N/A	NP_001280624.1	Q9UHD8-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEPTIN9	ENST00000329047.13	TSL:1 MANE Plus Clinical	c.-134G>C		5_prime_UTR	Exon 1 of 11	ENSP00000329161.8	Q9UHD8-2
	SEPTIN9	ENST00000427177.6	TSL:1 MANE Select	c.76+12996G>C		intron	N/A	ENSP00000391249.1	Q9UHD8-1
	SEPTIN9	ENST00000873888.1		c.76+12996G>C		intron	N/A	ENSP00000543947.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Amyotrophic neuralgia (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	20
DANN	Benign	0.92
PhyloP100		7.2
PromoterAI		-0.086	Neutral
Mutation Taster		=36/264	disease causing (ClinVar)

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: rs80338760; hg19: chr17-75316275;