Genetic Variant ENST00000299333:c.*1007dupT (chr11-123632791-C-CA) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The ENST00000299333.8(SCN3B):c.*1007dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000739 in 151,626 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00073 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0052 ( 0 hom. )

Consequence

SCN3B
ENST00000299333.8 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.475

Publications

0 publications found

Variant links:

Genes affected

SCN3B (HGNC:20665): (sodium voltage-gated channel beta subunit 3) Voltage-gated sodium channels are transmembrane glycoprotein complexes composed of a large alpha subunit and one or more regulatory beta subunits. They are responsible for the generation and propagation of action potentials in neurons and muscle. This gene encodes one member of the sodium channel beta subunit gene family, and influences the inactivation kinetics of the sodium channel. Two alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jul 2008]

SCN3B Gene-Disease associations (from GenCC):

familial atrial fibrillation
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Brugada syndrome 7
Inheritance: AD, Unknown Classification: LIMITED Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
Brugada syndrome 1
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

SCN3B links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 111 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000299333.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN3B	NM_001040151.2	MANE Select	c.*1007dupT		3_prime_UTR	Exon 7 of 7	NP_001035241.1	Q9NY72
	SCN3B	NM_018400.4		c.*1007dupT		3_prime_UTR	Exon 6 of 6	NP_060870.1	Q9NY72

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SCN3B	ENST00000299333.8	TSL:1 MANE Select	c.*1007dupT	3_prime_UTR	Exon 7 of 7	ENSP00000299333.3	Q9NY72
SCN3B	ENST00000392770.6	TSL:1	c.*1007dupT	3_prime_UTR	Exon 6 of 6	ENSP00000376523.2	Q9NY72
SCN3B	ENST00000530277.5	TSL:1	c.*1351dupT	3_prime_UTR	Exon 6 of 6	ENSP00000432785.1	Q9NY72

Frequencies

GnomAD3 genomes

AF:

0.000734

AC:

111

AN:

151318

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000316

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000132

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00163

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.00112

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00521

AC:

AN:

192

Hom.:

Cov.:

AF XY:

0.00685

AC XY:

AN XY:

146

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00649

AC:

AN:

154

Other (OTH)

AF:

0.00

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000733

AC:

111

AN:

151434

Hom.:

Cov.:

AF XY:

0.000797

AC XY:

AN XY:

73990

show subpopulations

African (AFR)

AF:

0.000315

AC:

AN:

41270

American (AMR)

AF:

0.000131

AC:

AN:

15210

Ashkenazi Jewish (ASJ)

AF:

0.000289

AC:

AN:

3464

East Asian (EAS)

AF:

0.000194

AC:

AN:

5152

South Asian (SAS)

AF:

0.00

AC:

AN:

4762

European-Finnish (FIN)

AF:

0.00163

AC:

AN:

10448

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00112

AC:

AN:

67828

Other (OTH)

AF:

0.00

AC:

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

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:

0.000864

Hom.:

Bravo

AF:

0.000559

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Brugada syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.47

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over