NM_001040151.2:c.*1956_*1959delTATT

Variant names:

• chr11-123631839-TAATA-T
• rs776449566
• NM_001040151.2:c.*1956_*1959delTATT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001040151.2(SCN3B):​c.*1956_*1959delTATT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000263 in 151,828 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.000026 (0 hom., cov: 32)
• Consequence: SCN3B NM_001040151.2 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.591
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040151.2. 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.*1956_*1959delTATT		3_prime_UTR	Exon 7 of 7	NP_001035241.1	Q9NY72
	SCN3B	NM_018400.4		c.*1956_*1959delTATT		3_prime_UTR	Exon 6 of 6	NP_060870.1	Q9NY72

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN3B	ENST00000299333.8	TSL:1 MANE Select	c.*1956_*1959delTATT		3_prime_UTR	Exon 7 of 7	ENSP00000299333.3	Q9NY72
	SCN3B	ENST00000392770.6	TSL:1	c.*1956_*1959delTATT		3_prime_UTR	Exon 6 of 6	ENSP00000376523.2	Q9NY72
	SCN3B	ENST00000530277.5	TSL:1	c.*2300_*2303delTATT		3_prime_UTR	Exon 6 of 6	ENSP00000432785.1	Q9NY72

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 151828 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000657

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: 0.0000442

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 151828 Hom.: 0 Cov.: 32 AF XY: 0.0000405 AC XY: 3 AN XY: 74162

African (AFR) AF: 0.00 AC: 0 AN: 41344

American (AMR) AF: 0.0000657 AC: 1 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10556

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000442 AC: 3 AN: 67940

Other (OTH) AF: 0.00 AC: 0 AN: 2074

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000529

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Brugada syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.59

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

Other links and lift over

dbSNP: rs776449566; hg19: chr11-123502547;