rs1062753

Positions:

• chr22-41996807-G-A

Variant summary

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

The ENST00000396425.8(SEPTIN3):​c.*2051G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 1,572,938 control chromosomes in the GnomAD database, including 68,377 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 0.29 (6937 hom., cov: 31)
  • Exomes 𝑓: 0.29 (61440 hom.)
• Consequence: SEPTIN3 ENST00000396425.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.222

Genes affected

SEPTIN3 (HGNC:10750): (septin 3) This gene belongs to the septin family of GTPases. Members of this family are required for cytokinesis. Expression is upregulated by retinoic acid in a human teratocarcinoma cell line. The specific function of this gene has not been determined. Alternative splicing of this gene results in several transcript variants encoding different isoforms. [provided by RefSeq, May 2018]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEPTIN3	NM_001363845.2	c.2506-95G>A		intron_variant		ENST00000644076.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEPTIN3	ENST00000644076.2	c.2506-95G>A		intron_variant			NM_001363845.2

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44272 AN: 151938 Hom.: 6930 Cov.: 31

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.375

Gnomad EAS AF: 0.0521

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.298

GnomAD4 exome AF: 0.286 AC: 406971 AN: 1420882 Hom.: 61440 Cov.: 36 AF XY: 0.284 AC XY: 199492 AN XY: 702120

Gnomad4 AFR exome AF: 0.320

Gnomad4 AMR exome AF: 0.448

Gnomad4 ASJ exome AF: 0.365

Gnomad4 EAS exome AF: 0.0421

Gnomad4 SAS exome AF: 0.245

Gnomad4 FIN exome AF: 0.137

Gnomad4 NFE exome AF: 0.297

Gnomad4 OTH exome AF: 0.284

GnomAD4 genome AF: 0.291 AC: 44301 AN: 152056 Hom.: 6937 Cov.: 31 AF XY: 0.282 AC XY: 20934 AN XY: 74348

Gnomad4 AFR AF: 0.322

Gnomad4 AMR AF: 0.367

Gnomad4 ASJ AF: 0.375

Gnomad4 EAS AF: 0.0511

Gnomad4 SAS AF: 0.243

Gnomad4 FIN AF: 0.126

Gnomad4 NFE AF: 0.298

Gnomad4 OTH AF: 0.294

Alfa AF: 0.297 Hom.: 14183

Bravo AF: 0.312

Asia WGS AF: 0.179 AC: 624 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.0
DANN	Benign	0.67

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: rs1062753; hg19: chr22-42392811; COSMIC: COSV52173473; COSMIC: COSV52173473;