rs10496431

Positions:

• chr2-109548083-A-C
• chr2-109548083-A-G

Variant summary

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

The NM_144710.5(SEPTIN10):​c.1162-1846T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0643 in 152,176 control chromosomes in the GnomAD database, including 749 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 0.064 (749 hom., cov: 31)
• Consequence: SEPTIN10 NM_144710.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.321

Genes affected

SEPTIN10 (HGNC:14349): (septin 10) This gene encodes a member of the septin family of cytoskeletal proteins with GTPase activity. This protein localizes to the cytoplasm and nucleus and displays GTP-binding and GTPase activity. A pseudogene for this gene is located on chromosome 8. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2012]

RANBP2 (HGNC:9848): (RAN binding protein 2) RAN is a small GTP-binding protein of the RAS superfamily that is associated with the nuclear membrane and is thought to control a variety of cellular functions through its interactions with other proteins. This gene encodes a very large RAN-binding protein that immunolocalizes to the nuclear pore complex. The protein is a giant scaffold and mosaic cyclophilin-related nucleoporin implicated in the Ran-GTPase cycle. The encoded protein directly interacts with the E2 enzyme UBC9 and strongly enhances SUMO1 transfer from UBC9 to the SUMO1 target SP100. These findings place sumoylation at the cytoplasmic filaments of the nuclear pore complex and suggest that, for some substrates, modification and nuclear import are linked events. This gene is partially duplicated in a gene cluster that lies in a hot spot for recombination on chromosome 2q. [provided by RefSeq, Jul 2008]

SEPTIN10 (HGNC:):

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 (EAS) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEPTIN10	NM_144710.5	c.1162-1846T>G		intron_variant		ENST00000397712.7	NP_653311.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEPTIN10	ENST00000397712.7	c.1162-1846T>G		intron_variant		1	NM_144710.5	ENSP00000380824.2

Frequencies

GnomAD3 genomes AF: 0.0642 AC: 9760 AN: 152060 Hom.: 739 Cov.: 31

Gnomad AFR AF: 0.0505

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.0534

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.0845

Gnomad FIN AF: 0.0533

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0291

Gnomad OTH AF: 0.0688

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

GnomAD4 genome AF: 0.0643 AC: 9786 AN: 152176 Hom.: 749 Cov.: 31 AF XY: 0.0689 AC XY: 5128 AN XY: 74402

Gnomad4 AFR AF: 0.0505

Gnomad4 AMR AF: 0.205

Gnomad4 ASJ AF: 0.0534

Gnomad4 EAS AF: 0.240

Gnomad4 SAS AF: 0.0842

Gnomad4 FIN AF: 0.0533

Gnomad4 NFE AF: 0.0291

Gnomad4 OTH AF: 0.0676

Alfa AF: 0.0657 Hom.: 437

Bravo AF: 0.0813

Asia WGS AF: 0.149 AC: 517 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	7.2
DANN	Benign	0.74

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: rs10496431; hg19: chr2-110305660;