17-77307076-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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 id is 1193355.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 467 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEPTIN9	NM_001113491.2	c.20-65T>C		intron_variant		ENST00000427177.6
SEPTIN9	NM_001113492.2	c.-473-65T>C		intron_variant
SEPTIN9	NM_001293695.2	c.19+25522T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEPTIN9	ENST00000427177.6	c.20-65T>C		intron_variant		1	NM_001113491.2	A1

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

Gnomad4 AFR exome AF: 0.00929

Gnomad4 AMR exome AF: 0.000944

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000484

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000317

Gnomad4 OTH exome AF: 0.000738

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

Gnomad4 AFR AF: 0.0105

Gnomad4 AMR AF: 0.00170

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00173 Hom.: 0

Bravo AF: 0.00332

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 26, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	6.6
Dann	Benign	0.70

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

Publications

LitVar

Other links and lift over

dbSNP: rs138141924; hg19: chr17-75303158;