12-51705632-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001330260.2(SCN8A):c.1341+9T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000162 in 1,606,024 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000083 ( 0 hom. )

Consequence

SCN8A
NM_001330260.2 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.114

Publications

0 publications found

Variant links:

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]

SCN8A Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
developmental and epileptic encephalopathy, 13
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
cognitive impairment with or without cerebellar ataxia
Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
seizures, benign familial infantile, 5
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
benign familial infantile epilepsy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
infantile convulsions and choreoathetosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
undetermined early-onset epileptic encephalopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
myoclonus, familial, 2
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

SCN8A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 12-51705632-T-C is Benign according to our data. Variant chr12-51705632-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 461332.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SCN8A	NM_001330260.2 link	c.1341+9T>C	intron_variant	Intron 10 of 26	ENST00000627620.5	NP_001317189.1	Q9UQD0-2Q6B4S4
SCN8A	NM_014191.4 link	c.1341+9T>C	intron_variant	Intron 10 of 26	ENST00000354534.11	NP_055006.1	Q9UQD0-1
SCN8A	NM_001177984.3 link	c.1341+9T>C	intron_variant	Intron 10 of 25		NP_001171455.1	Q9UQD0-5
SCN8A	NM_001369788.1 link	c.1341+9T>C	intron_variant	Intron 10 of 25		NP_001356717.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SCN8A	ENST00000354534.11 link	c.1341+9T>C	intron_variant	Intron 10 of 26	1	NM_014191.4	ENSP00000346534.4	Q9UQD0-1
SCN8A	ENST00000627620.5 link	c.1341+9T>C	intron_variant	Intron 10 of 26	5	NM_001330260.2	ENSP00000487583.2	Q9UQD0-2
SCN8A	ENST00000599343.5 link	c.1341+9T>C	intron_variant	Intron 9 of 25	5		ENSP00000476447.3	Q9UQD0-3
SCN8A	ENST00000355133.7 link	c.1341+9T>C	intron_variant	Intron 9 of 24	1		ENSP00000347255.4	Q9UQD0-5

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000208

AC:

AN:

240072

AF XY:

0.0000308

show subpopulations

Gnomad AFR exome

AF:

0.000340

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000825

AC:

AN:

1453818

Hom.:

Cov.:

AF XY:

0.0000111

AC XY:

AN XY:

722734

show subpopulations

African (AFR)

AF:

0.000330

AC:

AN:

33362

American (AMR)

AF:

0.00

AC:

AN:

43992

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25966

East Asian (EAS)

AF:

0.00

AC:

AN:

39612

South Asian (SAS)

AF:

0.00

AC:

AN:

85172

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53206

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1106610

Other (OTH)

AF:

0.0000166

AC:

AN:

60144

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.000314

AC:

AN:

41460

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5202

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68034

Other (OTH)

AF:

0.000478

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000987

Hom.:

Bravo

AF:

0.0000718

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Developmental and epileptic encephalopathy

Benign:1

Dec 17, 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

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

(source)

DANN

Benign

0.81

PhyloP100

0.11

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over