17-77281386-G-A

Variant names:

• chr17-77281386-G-A
• rs373918368
• ENST00000589070.1:c.31+580G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000589070.1(SEPTIN9):​c.31+580G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000713 in 561,140 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000071 (0 hom.)
• Consequence: SEPTIN9 ENST00000589070.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.136
• Publications: 0 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000589070.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEPTIN9-DT	NR_136503.1		n.286+226C>T		intron	N/A
	SEPTIN9	NM_001113491.2	MANE Select	c.-150G>A		upstream_gene	N/A	NP_001106963.1	Q9UHD8-1
	SEPTIN9	NM_001293695.2		c.-150G>A		upstream_gene	N/A	NP_001280624.1	Q9UHD8-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEPTIN9	ENST00000589070.1	TSL:3	c.31+580G>A		intron	N/A	ENSP00000465332.1	K7EJV0
	SEPTIN9-DT	ENST00000581153.1	TSL:2	n.286+226C>T		intron	N/A
	SEPTIN9-DT	ENST00000581657.2	TSL:3	n.491+226C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000713 AC: 4 AN: 561140 Hom.: 0 Cov.: 8 AF XY: 0.00000686 AC XY: 2 AN XY: 291656

African (AFR) AF: 0.00 AC: 0 AN: 11408

American (AMR) AF: 0.00 AC: 0 AN: 20280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14720

East Asian (EAS) AF: 0.00 AC: 0 AN: 25208

South Asian (SAS) AF: 0.00 AC: 0 AN: 47566

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29722

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2256

European-Non Finnish (NFE) AF: 0.00000525 AC: 2 AN: 380834

Other (OTH) AF: 0.0000686 AC: 2 AN: 29146

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 9

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.7
DANN	Benign	0.94
PhyloP100		-0.14
PromoterAI		0.0094	Neutral

Splicing

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

Other links and lift over

dbSNP: rs373918368; hg19: chr17-75277468;