chr17-77307216-T-C

Variant names:

• chr17-77307216-T-C
• rs4789439
• NM_001113491.2:c.76+19T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001113491.2(SEPTIN9):​c.76+19T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.865 in 1,610,688 control chromosomes in the GnomAD database, including 603,506 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.88 (59077 hom., cov: 33)
  • Exomes 𝑓: 0.86 (544429 hom.)
• Consequence: SEPTIN9 NM_001113491.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0360
• Publications: 9 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 17-77307216-T-C is Benign according to our data. Variant chr17-77307216-T-C is described in ClinVar as Benign. ClinVar VariationId is 518264.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.964 is higher than 0.05.

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.76+19T>C		intron	N/A	NP_001106963.1	Q9UHD8-1
	SEPTIN9	NM_001293695.2		c.19+25662T>C		intron	N/A	NP_001280624.1	Q9UHD8-7
	SEPTIN9	NM_001113492.2		c.-417+19T>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.76+19T>C		intron	N/A	ENSP00000391249.1	Q9UHD8-1
	SEPTIN9	ENST00000873888.1		c.76+19T>C		intron	N/A	ENSP00000543947.1
	SEPTIN9	ENST00000873887.1		c.76+19T>C		intron	N/A	ENSP00000543946.1

Frequencies

GnomAD3 genomes AF: 0.880 AC: 133857 AN: 152142 Hom.: 59014 Cov.: 33

Gnomad AFR AF: 0.909

Gnomad AMI AF: 0.925

Gnomad AMR AF: 0.877

Gnomad ASJ AF: 0.768

Gnomad EAS AF: 0.987

Gnomad SAS AF: 0.929

Gnomad FIN AF: 0.916

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.852

Gnomad OTH AF: 0.852

GnomAD2 exomes AF: 0.885 AC: 219534 AN: 248028 AF XY: 0.884

Gnomad AFR exome AF: 0.907

Gnomad AMR exome AF: 0.913

Gnomad ASJ exome AF: 0.751

Gnomad EAS exome AF: 0.989

Gnomad FIN exome AF: 0.916

Gnomad NFE exome AF: 0.850

Gnomad OTH exome AF: 0.863

GnomAD4 exome AF: 0.863 AC: 1258711 AN: 1458428 Hom.: 544429 Cov.: 36 AF XY: 0.865 AC XY: 627670 AN XY: 725698

African (AFR) AF: 0.910 AC: 30430 AN: 33434

American (AMR) AF: 0.908 AC: 40618 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.756 AC: 19745 AN: 26114

East Asian (EAS) AF: 0.983 AC: 39019 AN: 39698

South Asian (SAS) AF: 0.935 AC: 80650 AN: 86224

European-Finnish (FIN) AF: 0.915 AC: 48369 AN: 52850

Middle Eastern (MID) AF: 0.857 AC: 4939 AN: 5766

European-Non Finnish (NFE) AF: 0.850 AC: 943161 AN: 1109356

Other (OTH) AF: 0.859 AC: 51780 AN: 60264

GnomAD4 genome AF: 0.880 AC: 133983 AN: 152260 Hom.: 59077 Cov.: 33 AF XY: 0.884 AC XY: 65794 AN XY: 74436

African (AFR) AF: 0.909 AC: 37757 AN: 41542

American (AMR) AF: 0.877 AC: 13427 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.768 AC: 2666 AN: 3470

East Asian (EAS) AF: 0.987 AC: 5115 AN: 5182

South Asian (SAS) AF: 0.930 AC: 4483 AN: 4820

European-Finnish (FIN) AF: 0.916 AC: 9736 AN: 10624

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.852 AC: 57902 AN: 67996

Other (OTH) AF: 0.854 AC: 1804 AN: 2112

Alfa AF: 0.857 Hom.: 9488

Bravo AF: 0.875

Asia WGS AF: 0.958 AC: 3332 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.8
DANN	Benign	0.42
PhyloP100		0.036
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: rs4789439; hg19: chr17-75303298;