17-77317253-A-G

Position:

• chr17-77317253-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001113491.2(SEPTIN9):​c.76+10056A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 151,920 control chromosomes in the GnomAD database, including 14,002 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.41 (14002 hom., cov: 31)
• Consequence: SEPTIN9 NM_001113491.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0480

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]

SEPTIN9 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEPTIN9	NM_001113491.2	c.76+10056A>G		intron_variant		ENST00000427177.6	NP_001106963.1
SEPTIN9	NM_001293695.2	c.19+35699A>G		intron_variant			NP_001280624.1
SEPTIN9	NM_001113492.2	c.-417+10056A>G		intron_variant			NP_001106964.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEPTIN9	ENST00000427177.6	c.76+10056A>G		intron_variant		1	NM_001113491.2	ENSP00000391249.1

Frequencies

GnomAD3 genomes AF: 0.408 AC: 61901 AN: 151802 Hom.: 14005 Cov.: 31

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.548

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.408

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.408 AC: 61913 AN: 151920 Hom.: 14002 Cov.: 31 AF XY: 0.413 AC XY: 30673 AN XY: 74234

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.500

Gnomad4 ASJ AF: 0.451

Gnomad4 EAS AF: 0.531

Gnomad4 SAS AF: 0.487

Gnomad4 FIN AF: 0.517

Gnomad4 NFE AF: 0.480

Gnomad4 OTH AF: 0.411

Alfa AF: 0.475 Hom.: 34927

Bravo AF: 0.396

Asia WGS AF: 0.452 AC: 1568 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.7
DANN	Benign	0.54

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: rs4788985; hg19: chr17-75313335;