rs80338762

chr17-77402314-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_001113491.2(SEPTIN9):c.332C>T(p.Ser111Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SEPTIN9 NM_001113491.2 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1 O:1
• Conservation: PhyloP100: 7.40

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 17-77402314-C-T is Pathogenic according to our data. Variant chr17-77402314-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 5864.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-77402314-C-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEPTIN9	NM_001113491.2	c.332C>T	p.Ser111Phe	missense_variant	3/12	ENST00000427177.6
SEPTIN9	NM_006640.5	c.278C>T	p.Ser93Phe	missense_variant	2/11	ENST00000329047.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEPTIN9	ENST00000427177.6	c.332C>T	p.Ser111Phe	missense_variant	3/12	1	NM_001113491.2	A1
SEPTIN9	ENST00000329047.13	c.278C>T	p.Ser93Phe	missense_variant	2/11	1	NM_006640.5	P3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1 Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Amyotrophic neuralgia Pathogenic:1 Other:1

Pathogenic, no assertion criteria provided	literature only	OMIM	May 19, 2009	- -
not provided, no classification provided	literature only	GeneReviews	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.24
Cadd	Pathogenic	28
Dann	Uncertain	1.0
Eigen	Uncertain	0.65
Eigen_PC	Pathogenic	0.66
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D;D;D;D;.;D;D;D
M_CAP	Benign	0.069	D
MetaRNN	Uncertain	0.72	D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.79	T
MutationTaster	Benign	1.0	A;A;A;A;A;A;A;A;A;A
PrimateAI	Uncertain	0.78	T
Sift4G	Uncertain	0.0040	D;D;D;D;D;D;D;D
Polyphen		1.0	.;D;D;D;D;.;D;.
Vest4		0.91, 0.90, 0.93, 0.94, 0.89
MutPred		0.59		.;Gain of catalytic residue at S111 (P = 0.007);.;.;.;.;.;.;
MVP		0.83
MPC		0.51
ClinPred		0.98	D
GERP RS		5.3
Varity_R		0.40
gMVP		0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs80338762; hg19: chr17-75398396;