3-38846530-T-C

Position:

• chr3-38846530-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001349253.2(SCN11A):​c.*164A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 611,804 control chromosomes in the GnomAD database, including 87,194 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.58 (26960 hom., cov: 33)
  • Exomes 𝑓: 0.51 (60234 hom.)
• Consequence: SCN11A NM_001349253.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.14

Genes affected

SCN11A (HGNC:10583): (sodium voltage-gated channel alpha subunit 11) Voltage-gated sodium channels are transmembrane glycoprotein complexes composed of a large alpha subunit with 24 transmembrane domains 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 alpha subunit gene family, and is highly expressed in nociceptive neurons of dorsal root ganglia and trigeminal ganglia. It mediates brain-derived neurotrophic factor-evoked membrane depolarization and is a major effector of peripheral inflammatory pain hypersensitivity. Mutations in this gene have been associated with hereditary sensory and autonomic neuropathy type VII and familial episodic pain syndrome-3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2017]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 3-38846530-T-C is Benign according to our data. Variant chr3-38846530-T-C is described in ClinVar as [Benign]. Clinvar id is 1178114.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN11A	NM_001349253.2	c.*164A>G		3_prime_UTR_variant	30/30	ENST00000302328.9	NP_001336182.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN11A	ENST00000302328.9	c.*164A>G		3_prime_UTR_variant	30/30	5	NM_001349253.2	ENSP00000307599	A2
SCN11A	ENST00000668754.1	c.*164A>G		3_prime_UTR_variant	33/33			ENSP00000499569	A2

Frequencies

GnomAD3 genomes AF: 0.581 AC: 88345 AN: 151982 Hom.: 26915 Cov.: 33

Gnomad AFR AF: 0.786

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.471

Gnomad ASJ AF: 0.556

Gnomad EAS AF: 0.546

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.505

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.547

GnomAD4 exome AF: 0.508 AC: 233469 AN: 459704 Hom.: 60234 Cov.: 4 AF XY: 0.503 AC XY: 121777 AN XY: 241870

Gnomad4 AFR exome AF: 0.775

Gnomad4 AMR exome AF: 0.466

Gnomad4 ASJ exome AF: 0.548

Gnomad4 EAS exome AF: 0.515

Gnomad4 SAS exome AF: 0.432

Gnomad4 FIN exome AF: 0.506

Gnomad4 NFE exome AF: 0.507

Gnomad4 OTH exome AF: 0.518

GnomAD4 genome AF: 0.582 AC: 88448 AN: 152100 Hom.: 26960 Cov.: 33 AF XY: 0.574 AC XY: 42690 AN XY: 74324

Gnomad4 AFR AF: 0.786

Gnomad4 AMR AF: 0.471

Gnomad4 ASJ AF: 0.556

Gnomad4 EAS AF: 0.547

Gnomad4 SAS AF: 0.421

Gnomad4 FIN AF: 0.505

Gnomad4 NFE AF: 0.510

Gnomad4 OTH AF: 0.548

Alfa AF: 0.517 Hom.: 34763

Bravo AF: 0.594

Asia WGS AF: 0.489 AC: 1701 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.77

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: rs4234133; hg19: chr3-38888021;