17-77307216-T-C

Position:

• chr17-77307216-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id is 518264.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-77307216-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.964 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEPTIN9	NM_001113491.2	c.76+19T>C		intron_variant		ENST00000427177.6	NP_001106963.1
SEPTIN9	NM_001293695.2	c.19+25662T>C		intron_variant			NP_001280624.1
SEPTIN9	NM_001113492.2	c.-417+19T>C		intron_variant			NP_001106964.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEPTIN9	ENST00000427177.6	c.76+19T>C		intron_variant		1	NM_001113491.2	ENSP00000391249.1

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

GnomAD3 exomes AF: 0.885 AC: 219534 AN: 248028 Hom.: 97502 AF XY: 0.884 AC XY: 119250 AN XY: 134922

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 SAS exome AF: 0.936

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

Gnomad4 AFR exome AF: 0.910

Gnomad4 AMR exome AF: 0.908

Gnomad4 ASJ exome AF: 0.756

Gnomad4 EAS exome AF: 0.983

Gnomad4 SAS exome AF: 0.935

Gnomad4 FIN exome AF: 0.915

Gnomad4 NFE exome AF: 0.850

Gnomad4 OTH exome AF: 0.859

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

Gnomad4 AFR AF: 0.909

Gnomad4 AMR AF: 0.877

Gnomad4 ASJ AF: 0.768

Gnomad4 EAS AF: 0.987

Gnomad4 SAS AF: 0.930

Gnomad4 FIN AF: 0.916

Gnomad4 NFE AF: 0.852

Gnomad4 OTH AF: 0.854

Alfa AF: 0.857 Hom.: 9488

Bravo AF: 0.875

Asia WGS AF: 0.958 AC: 3332 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 06, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.8
DANN	Benign	0.42

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: rs4789439; hg19: chr17-75303298;