NM_001113491.2:c.77-17967G>C

Variant names:

• chr17-77384092-G-C
• rs103550
• NM_001113491.2:c.77-17967G>C

Variant summary

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

The NM_001113491.2(SEPTIN9):​c.77-17967G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.68 in 152,088 control chromosomes in the GnomAD database, including 35,284 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 0.68 (35284 hom., cov: 32)
• Consequence: SEPTIN9 NM_001113491.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.11
• Publications: 4 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.713 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEPTIN9	NM_001113491.2	c.77-17967G>C		intron_variant	Intron 2 of 11	ENST00000427177.6	NP_001106963.1
SEPTIN9	NM_006640.5	c.23-17967G>C		intron_variant	Intron 1 of 10	ENST00000329047.13	NP_006631.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEPTIN9	ENST00000427177.6	c.77-17967G>C		intron_variant	Intron 2 of 11	1	NM_001113491.2	ENSP00000391249.1
SEPTIN9	ENST00000329047.13	c.23-17967G>C		intron_variant	Intron 1 of 10	1	NM_006640.5	ENSP00000329161.8

Frequencies

GnomAD3 genomes AF: 0.680 AC: 103364 AN: 151970 Hom.: 35240 Cov.: 32

Gnomad AFR AF: 0.720

Gnomad AMI AF: 0.678

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.693

Gnomad SAS AF: 0.641

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.682

Gnomad OTH AF: 0.687

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

GnomAD4 genome AF: 0.680 AC: 103459 AN: 152088 Hom.: 35284 Cov.: 32 AF XY: 0.677 AC XY: 50354 AN XY: 74336

African (AFR) AF: 0.720 AC: 29862 AN: 41496

American (AMR) AF: 0.629 AC: 9628 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.639 AC: 2216 AN: 3470

East Asian (EAS) AF: 0.693 AC: 3574 AN: 5160

South Asian (SAS) AF: 0.641 AC: 3089 AN: 4818

European-Finnish (FIN) AF: 0.612 AC: 6465 AN: 10572

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.682 AC: 46353 AN: 67950

Other (OTH) AF: 0.689 AC: 1457 AN: 2114

Alfa AF: 0.674 Hom.: 4309

Bravo AF: 0.684

Asia WGS AF: 0.683 AC: 2375 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.067
DANN	Benign	0.67
PhyloP100		-2.1
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: rs103550; hg19: chr17-75380174;