17-77281498-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NR_136503.1(SEPTIN9-DT):n.286+114G>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00161 in 1,545,440 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0085 (22 hom., cov: 33)
  • Exomes 𝑓: 0.00086 (15 hom.)
• Consequence: SEPTIN9-DT NR_136503.1 intron, non_coding_transcript
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.846

Genes affected

SEPTIN9-DT (HGNC:52818): (SEPTIN9 divergent transcript)

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 17-77281498-C-T is Benign according to our data. Variant chr17-77281498-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1196918.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00852 (1298/152258) while in subpopulation AFR AF= 0.0289 (1199/41556). AF 95% confidence interval is 0.0275. There are 22 homozygotes in gnomad4. There are 628 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 22 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEPTIN9-DT	NR_136503.1	n.286+114G>A		intron_variant, non_coding_transcript_variant
SEPTIN9	NM_001113491.2			upstream_gene_variant		ENST00000427177.6
SEPTIN9	NM_001293695.2			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEPTIN9-DT	ENST00000701682.1	n.443+114G>A		intron_variant, non_coding_transcript_variant
SEPTIN9	ENST00000427177.6			upstream_gene_variant		1	NM_001113491.2	A1

Frequencies

GnomAD3 genomes AF: 0.00852 AC: 1296 AN: 152142 Hom.: 22 Cov.: 33

Gnomad AFR AF: 0.0289

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00484

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00764

GnomAD3 exomes AF: 0.00189 AC: 269 AN: 142550 Hom.: 3 AF XY: 0.00135 AC XY: 104 AN XY: 77140

Gnomad AFR exome AF: 0.0378

Gnomad AMR exome AF: 0.00148

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000446

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000131

Gnomad OTH exome AF: 0.00121

GnomAD4 exome AF: 0.000858 AC: 1195 AN: 1393182 Hom.: 15 Cov.: 30 AF XY: 0.000730 AC XY: 502 AN XY: 687380

Gnomad4 AFR exome AF: 0.0297

Gnomad4 AMR exome AF: 0.00227

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000760

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000687

Gnomad4 OTH exome AF: 0.00204

GnomAD4 genome AF: 0.00852 AC: 1298 AN: 152258 Hom.: 22 Cov.: 33 AF XY: 0.00844 AC XY: 628 AN XY: 74448

Gnomad4 AFR AF: 0.0289

Gnomad4 AMR AF: 0.00483

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000883

Gnomad4 OTH AF: 0.00756

Alfa AF: 0.00427 Hom.: 1

Bravo AF: 0.0102

Asia WGS AF: 0.00144 AC: 5 AN: 3476

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

Aug 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	7.7
Dann	Benign	0.92
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs144505525; hg19: chr17-75277580;