17-77281351-T-G

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+261A>C 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 0.0367 in 536,186 control chromosomes in the GnomAD database, including 442 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.035 (101 hom., cov: 27)
  • Exomes 𝑓: 0.037 (341 hom.)
• Consequence: SEPTIN9-DT NR_136503.1 intron, non_coding_transcript
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.459

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=-0.8).
• BP6: Variant 17-77281351-T-G is Benign according to our data. Variant chr17-77281351-T-G is described in ClinVar as [Benign]. Clinvar id is 1255034.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0349 (4429/126886) while in subpopulation NFE AF= 0.0477 (2921/61218). AF 95% confidence interval is 0.0463. There are 101 homozygotes in gnomad4. There are 2156 alleles in male gnomad4 subpopulation. Median coverage is 27. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 101 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEPTIN9-DT	NR_136503.1	n.286+261A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEPTIN9-DT	ENST00000701682.1	n.443+261A>C		intron_variant, non_coding_transcript_variant
SEPTIN9	ENST00000589070.1	c.31+545T>G		intron_variant		3
SEPTIN9-DT	ENST00000581153.1	n.286+261A>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0349 AC: 4432 AN: 126854 Hom.: 101 Cov.: 27

Gnomad AFR AF: 0.0113

Gnomad AMI AF: 0.00988

Gnomad AMR AF: 0.0267

Gnomad ASJ AF: 0.0198

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0186

Gnomad FIN AF: 0.0947

Gnomad MID AF: 0.0144

Gnomad NFE AF: 0.0477

Gnomad OTH AF: 0.0217

GnomAD4 exome AF: 0.0373 AC: 15263 AN: 409300 Hom.: 341 AF XY: 0.0365 AC XY: 7886 AN XY: 216026

Gnomad4 AFR exome AF: 0.00679

Gnomad4 AMR exome AF: 0.0156

Gnomad4 ASJ exome AF: 0.0196

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0173

Gnomad4 FIN exome AF: 0.0645

Gnomad4 NFE exome AF: 0.0443

Gnomad4 OTH exome AF: 0.0326

GnomAD4 genome AF: 0.0349 AC: 4429 AN: 126886 Hom.: 101 Cov.: 27 AF XY: 0.0358 AC XY: 2156 AN XY: 60216

Gnomad4 AFR AF: 0.0113

Gnomad4 AMR AF: 0.0266

Gnomad4 ASJ AF: 0.0198

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0183

Gnomad4 FIN AF: 0.0947

Gnomad4 NFE AF: 0.0477

Gnomad4 OTH AF: 0.0216

Alfa AF: 0.0182 Hom.: 8

Bravo AF: 0.0256

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

Jul 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	4.3
Dann	Benign	0.19

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs564233160; hg19: chr17-75277433;