17-77281643-C-G

Variant names:

• chr17-77281643-C-G
• rs116581271
• NM_001113491.2:c.19+89C>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 2P and 8B. PM2 BP4_Strong BS2

The NM_001113491.2(SEPTIN9):​c.19+89C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000433 in 1,154,890 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: 33)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: SEPTIN9 NM_001113491.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.464
• 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 -6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001113491.2. 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	NM_001113491.2	MANE Select	c.19+89C>G		intron	N/A	NP_001106963.1	Q9UHD8-1
	SEPTIN9	NM_001293695.2		c.19+89C>G		intron	N/A	NP_001280624.1	Q9UHD8-7
	SEPTIN9-DT	NR_136503.1		n.255G>C		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEPTIN9	ENST00000427177.6	TSL:1 MANE Select	c.19+89C>G		intron	N/A	ENSP00000391249.1	Q9UHD8-1
	SEPTIN9	ENST00000873888.1		c.19+89C>G		intron	N/A	ENSP00000543947.1
	SEPTIN9	ENST00000873887.1		c.19+89C>G		intron	N/A	ENSP00000543946.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000433 AC: 5 AN: 1154890 Hom.: 0 Cov.: 15 AF XY: 0.00000526 AC XY: 3 AN XY: 569904

African (AFR) AF: 0.00 AC: 0 AN: 23288

American (AMR) AF: 0.00 AC: 0 AN: 28160

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20886

East Asian (EAS) AF: 0.00 AC: 0 AN: 28952

South Asian (SAS) AF: 0.00 AC: 0 AN: 67096

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41886

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4338

European-Non Finnish (NFE) AF: 0.00000561 AC: 5 AN: 891296

Other (OTH) AF: 0.00 AC: 0 AN: 48988

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.0
DANN	Benign	0.73
PhyloP100		-0.46
PromoterAI		0.090	Neutral
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

Other links and lift over

dbSNP: rs116581271; hg19: chr17-75277725;