rs587780452

Variant names:

• chr12-51751340-TCTTA-T
• rs587780452
• NM_001330260.2:c.2132-8_2132-5delTACT

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_001330260.2(SCN8A):​c.2132-8_2132-5delTACT variant causes a splice region, intron change. The variant allele was found at a frequency of 0.00000558 in 1,434,338 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000056 (0 hom.)
• Consequence: SCN8A NM_001330260.2 splice_region, intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.19

Genes affected

SCN8A (HGNC:10596): (sodium voltage-gated channel alpha subunit 8) This gene encodes a member of the sodium channel alpha subunit gene family. The encoded protein forms the ion pore region of the voltage-gated sodium channel. This protein is essential for the rapid membrane depolarization that occurs during the formation of the action potential in excitable neurons. Mutations in this gene are associated with cognitive disability, pancerebellar atrophy and ataxia. Alternate splicing results in multiple transcript variants.[provided by RefSeq, May 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP6: Variant 12-51751340-TCTTA-T is Benign according to our data. Variant chr12-51751340-TCTTA-T is described in ClinVar as [Likely_benign]. Clinvar id is 130243.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN8A	NM_001330260.2	c.2132-8_2132-5delTACT		splice_region_variant, intron_variant	Intron 13 of 26	ENST00000627620.5	NP_001317189.1
SCN8A	NM_014191.4	c.2132-8_2132-5delTACT		splice_region_variant, intron_variant	Intron 13 of 26	ENST00000354534.11	NP_055006.1
SCN8A	NM_001177984.3	c.2132-8_2132-5delTACT		splice_region_variant, intron_variant	Intron 13 of 25		NP_001171455.1
SCN8A	NM_001369788.1	c.2132-8_2132-5delTACT		splice_region_variant, intron_variant	Intron 13 of 25		NP_001356717.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN8A	ENST00000354534.11	c.2132-14_2132-11delCTTA		intron_variant	Intron 13 of 26	1	NM_014191.4	ENSP00000346534.4
SCN8A	ENST00000627620.5	c.2132-14_2132-11delCTTA		intron_variant	Intron 13 of 26	5	NM_001330260.2	ENSP00000487583.2
SCN8A	ENST00000599343.5	c.2165-14_2165-11delCTTA		intron_variant	Intron 12 of 25	5		ENSP00000476447.3
SCN8A	ENST00000355133.7	c.2132-14_2132-11delCTTA		intron_variant	Intron 12 of 24	1		ENSP00000347255.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000822 AC: 2 AN: 243182 Hom.: 0 AF XY: 0.00000759 AC XY: 1 AN XY: 131796

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000181

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000558 AC: 8 AN: 1434338 Hom.: 0 AF XY: 0.00000700 AC XY: 5 AN XY: 713906

Gnomad4 AFR exome AF: 0.0000304

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000642

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

May 20, 2014

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Early infantile epileptic encephalopathy with suppression bursts Benign:1

May 08, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

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: rs587780452; hg19: chr12-52145124;