rs39588

Positions:

• chr5-132763443-C-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEPTIN8	NM_001098811.2	c.534+263G>C		intron_variant		ENST00000378719.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEPTIN8	ENST00000378719.7	c.534+263G>C		intron_variant		1	NM_001098811.2	P3

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

Gnomad4 AFR AF: 0.787

Gnomad4 AMR AF: 0.293

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.734

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.290

Gnomad4 NFE AF: 0.124

Gnomad4 OTH AF: 0.293

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.65

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: rs39588; hg19: chr5-132099135;