17-77281386-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NR_136503.1(SEPTIN9-DT):n.286+226C>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 0.0419 in 702,090 control chromosomes in the GnomAD database, including 723 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.036 (121 hom., cov: 31)
  • Exomes 𝑓: 0.043 (602 hom.)
• Consequence: SEPTIN9-DT NR_136503.1 intron, non_coding_transcript
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.136

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=-0.79).
• BP6: Variant 17-77281386-G-T is Benign according to our data. Variant chr17-77281386-G-T is described in ClinVar as [Benign]. Clinvar id is 1227821.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEPTIN9-DT	NR_136503.1	n.286+226C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEPTIN9-DT	ENST00000701682.1	n.443+226C>A		intron_variant, non_coding_transcript_variant
SEPTIN9	ENST00000589070.1	c.31+580G>T		intron_variant		3
SEPTIN9-DT	ENST00000581153.1	n.286+226C>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0356 AC: 5027 AN: 141144 Hom.: 122 Cov.: 31

Gnomad AFR AF: 0.00942

Gnomad AMI AF: 0.0824

Gnomad AMR AF: 0.0259

Gnomad ASJ AF: 0.0490

Gnomad EAS AF: 0.000212

Gnomad SAS AF: 0.0291

Gnomad FIN AF: 0.0354

Gnomad MID AF: 0.0171

Gnomad NFE AF: 0.0557

Gnomad OTH AF: 0.0365

GnomAD4 exome AF: 0.0434 AC: 24363 AN: 560866 Hom.: 602 Cov.: 8 AF XY: 0.0435 AC XY: 12677 AN XY: 291540

Gnomad4 AFR exome AF: 0.00798

Gnomad4 AMR exome AF: 0.0168

Gnomad4 ASJ exome AF: 0.0447

Gnomad4 EAS exome AF: 0.0000793

Gnomad4 SAS exome AF: 0.0325

Gnomad4 FIN exome AF: 0.0406

Gnomad4 NFE exome AF: 0.0506

Gnomad4 OTH exome AF: 0.0406

GnomAD4 genome AF: 0.0356 AC: 5024 AN: 141224 Hom.: 121 Cov.: 31 AF XY: 0.0332 AC XY: 2272 AN XY: 68470

Gnomad4 AFR AF: 0.00940

Gnomad4 AMR AF: 0.0259

Gnomad4 ASJ AF: 0.0490

Gnomad4 EAS AF: 0.000212

Gnomad4 SAS AF: 0.0287

Gnomad4 FIN AF: 0.0354

Gnomad4 NFE AF: 0.0557

Gnomad4 OTH AF: 0.0362

Alfa AF: 0.0178 Hom.: 9

Asia WGS AF: 0.0100 AC: 34 AN: 3406

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 06, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	4.1
Dann	Benign	0.85

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs373918368; hg19: chr17-75277468;