3-38846479-T-A

Position:

• chr3-38846479-T-A

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.*215A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 551,160 control chromosomes in the GnomAD database, including 79,721 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.58 (26965 hom., cov: 33)
  • Exomes 𝑓: 0.51 (52756 hom.)
• Consequence: SCN11A NM_001349253.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.153

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=-0.9).
• BP6: Variant 3-38846479-T-A is Benign according to our data. Variant chr3-38846479-T-A is described in ClinVar as [Benign]. Clinvar id is 1273152.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.*215A>T		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	c.*215A>T		3_prime_UTR_variant	30/30	5	NM_001349253.2	ENSP00000307599.3
SCN11A	ENST00000668754	c.*215A>T		3_prime_UTR_variant	33/33			ENSP00000499569.1

Frequencies

GnomAD3 genomes AF: 0.581 AC: 88361 AN: 152028 Hom.: 26920 Cov.: 33

Gnomad AFR AF: 0.786

Gnomad AMI AF: 0.586

Gnomad AMR AF: 0.471

Gnomad ASJ AF: 0.556

Gnomad EAS AF: 0.546

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.504

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.546

GnomAD4 exome AF: 0.509 AC: 203216 AN: 399014 Hom.: 52756 Cov.: 3 AF XY: 0.505 AC XY: 105140 AN XY: 208274

Gnomad4 AFR exome AF: 0.776

Gnomad4 AMR exome AF: 0.467

Gnomad4 ASJ exome AF: 0.548

Gnomad4 EAS exome AF: 0.518

Gnomad4 SAS exome AF: 0.429

Gnomad4 FIN exome AF: 0.512

Gnomad4 NFE exome AF: 0.507

Gnomad4 OTH exome AF: 0.519

GnomAD4 genome AF: 0.581 AC: 88464 AN: 152146 Hom.: 26965 Cov.: 33 AF XY: 0.574 AC XY: 42708 AN XY: 74366

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: 0.504

Gnomad4 NFE AF: 0.510

Gnomad4 OTH AF: 0.547

Alfa AF: 0.446 Hom.: 1336

Bravo AF: 0.594

Asia WGS AF: 0.490 AC: 1702 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	-0.90
CADD	Benign	3.0
DANN	Benign	0.55

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: rs4234134; hg19: chr3-38887970;