ENST00000530277:c.*352T>A

Variant names:

• chr11-123633791-A-T
• rs1057524334
• ENST00000530277.5:c.*352T>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The ENST00000530277.5(SCN3B):​c.*352T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000511 in 195,622 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000051 (0 hom.)
• Consequence: SCN3B ENST00000530277.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.22
• 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 11-123633791-A-T is Benign according to our data. Variant chr11-123633791-A-T is described in ClinVar as Likely_benign. ClinVar VariationId is 392040.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000530277.5. 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.*23-15T>A		intron	N/A	NP_001035241.1	Q9NY72
	SCN3B	NM_018400.4		c.*23-15T>A		intron	N/A	NP_060870.1	Q9NY72

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN3B	ENST00000530277.5	TSL:1	c.*352T>A		3_prime_UTR	Exon 6 of 6	ENSP00000432785.1	Q9NY72
	SCN3B	ENST00000299333.8	TSL:1 MANE Select	c.*23-15T>A		intron	N/A	ENSP00000299333.3	Q9NY72
	SCN3B	ENST00000392770.6	TSL:1	c.*23-15T>A		intron	N/A	ENSP00000376523.2	Q9NY72

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000511 AC: 1 AN: 195622 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 105602

African (AFR) AF: 0.00 AC: 0 AN: 5574

American (AMR) AF: 0.0000928 AC: 1 AN: 10780

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4864

East Asian (EAS) AF: 0.00 AC: 0 AN: 8962

South Asian (SAS) AF: 0.00 AC: 0 AN: 36216

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8728

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 706

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 109956

Other (OTH) AF: 0.00 AC: 0 AN: 9836

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	11
DANN	Benign	0.76
PhyloP100		1.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs1057524334; hg19: chr11-123504499;