NM_001113491.2:c.20-65T>C

Variant names:

• chr17-77307076-T-C
• rs138141924
• NM_001113491.2:c.20-65T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001113491.2(SEPTIN9):​c.20-65T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000588 in 1,431,954 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0031 (3 hom., cov: 33)
  • Exomes 𝑓: 0.00029 (1 hom.)
• Consequence: SEPTIN9 NM_001113491.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.166
• 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 17-77307076-T-C is Benign according to our data. Variant chr17-77307076-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1193355.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 470 AD gene.

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.20-65T>C		intron	N/A	NP_001106963.1	Q9UHD8-1
	SEPTIN9	NM_001293695.2		c.19+25522T>C		intron	N/A	NP_001280624.1	Q9UHD8-7
	SEPTIN9	NM_001113492.2		c.-473-65T>C		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.20-65T>C		intron	N/A	ENSP00000391249.1	Q9UHD8-1
	SEPTIN9	ENST00000873888.1		c.20-65T>C		intron	N/A	ENSP00000543947.1
	SEPTIN9	ENST00000873887.1		c.20-65T>C		intron	N/A	ENSP00000543946.1

Frequencies

GnomAD3 genomes AF: 0.00307 AC: 467 AN: 152202 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.0104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00287

GnomAD4 exome AF: 0.000291 AC: 372 AN: 1279634 Hom.: 1 AF XY: 0.000232 AC XY: 150 AN XY: 645998

African (AFR) AF: 0.00929 AC: 277 AN: 29826

American (AMR) AF: 0.000944 AC: 42 AN: 44496

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24992

East Asian (EAS) AF: 0.00 AC: 0 AN: 38830

South Asian (SAS) AF: 0.0000484 AC: 4 AN: 82604

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53238

Middle Eastern (MID) AF: 0.00111 AC: 6 AN: 5404

European-Non Finnish (NFE) AF: 0.00000317 AC: 3 AN: 946056

Other (OTH) AF: 0.000738 AC: 40 AN: 54188

GnomAD4 genome AF: 0.00309 AC: 470 AN: 152320 Hom.: 3 Cov.: 33 AF XY: 0.00282 AC XY: 210 AN XY: 74482

African (AFR) AF: 0.0105 AC: 436 AN: 41560

American (AMR) AF: 0.00170 AC: 26 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68024

Other (OTH) AF: 0.00284 AC: 6 AN: 2112

Alfa AF: 0.00173 Hom.: 0

Bravo AF: 0.00332

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.6
DANN	Benign	0.70
PhyloP100		0.17
Mutation Taster		=100/0	polymorphism

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: rs138141924; hg19: chr17-75303158;