rs39588

Variant names:

• chr5-132763443-C-G
• rs39588
• NM_001098811.2:c.534+263G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001098811.2(SEPTIN8):​c.534+263G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 152,022 control chromosomes in the GnomAD database, including 16,245 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 0.36 (16245 hom., cov: 32)
• Consequence: SEPTIN8 NM_001098811.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.382
• Publications: 6 publications found

Genes affected

SEPTIN8 (HGNC:16511): (septin 8) This gene is a member of the septin family of nucleotide binding proteins, originally described in yeast as cell division cycle regulatory proteins. Septins are highly conserved in yeast, Drosophila, and mouse, and appear to regulate cytoskeletal organization. Disruption of septin function disturbs cytokinesis and results in large multinucleate or polyploid cells. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098811.2. 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
	SEPTIN8	NM_001098811.2	MANE Select	c.534+263G>C		intron	N/A	NP_001092281.1	Q92599-1
	SEPTIN8	NM_001098812.2		c.534+263G>C		intron	N/A	NP_001092282.1	Q92599-4
	SEPTIN8	NM_001300798.2		c.528+263G>C		intron	N/A	NP_001287727.1	A6NFQ9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEPTIN8	ENST00000378719.7	TSL:1 MANE Select	c.534+263G>C		intron	N/A	ENSP00000367991.2	Q92599-1
	SEPTIN8	ENST00000296873.11	TSL:1	c.534+263G>C		intron	N/A	ENSP00000296873.7	Q92599-2
	SEPTIN8	ENST00000448933.5	TSL:1	c.354+263G>C		intron	N/A	ENSP00000399840.1	Q92599-3

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54206 AN: 151904 Hom.: 16202 Cov.: 32

Gnomad AFR AF: 0.786

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.735

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.290

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

GnomAD4 genome AF: 0.357 AC: 54320 AN: 152022 Hom.: 16245 Cov.: 32 AF XY: 0.362 AC XY: 26910 AN XY: 74288

African (AFR) AF: 0.787 AC: 32602 AN: 41450

American (AMR) AF: 0.293 AC: 4474 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 487 AN: 3470

East Asian (EAS) AF: 0.734 AC: 3781 AN: 5152

South Asian (SAS) AF: 0.166 AC: 799 AN: 4814

European-Finnish (FIN) AF: 0.290 AC: 3065 AN: 10564

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.124 AC: 8429 AN: 67980

Other (OTH) AF: 0.293 AC: 618 AN: 2108

Alfa AF: 0.251 Hom.: 1180

Bravo AF: 0.384

Asia WGS AF: 0.429 AC: 1492 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.65
PhyloP100		-0.38
Mutation Taster		=100/0	polymorphism (auto)

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: rs39588; hg19: chr5-132099135;