rs6801957

Variant names:

• chr3-38725824-T-C
• rs6801957
• NM_006514.4:c.3088-510A>G

Your query was ambiguous. Multiple possible variants found:

• chr3-38725824-T-C
• chr3-38725824-T-A
• chr3-38725824-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006514.4(SCN10A):​c.3088-510A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.669 in 152,200 control chromosomes in the GnomAD database, including 35,019 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.67 (35019 hom., cov: 33)
• Consequence: SCN10A NM_006514.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.576
• Publications: 90 publications found

Genes affected

SCN10A (HGNC:10582): (sodium voltage-gated channel alpha subunit 10) The protein encoded by this gene is a tetrodotoxin-resistant voltage-gated sodium channel alpha subunit. The properties of the channel formed by the encoded transmembrane protein can be altered by interaction with different beta subunits. This protein may be involved in the onset of pain associated with peripheral neuropathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

SCN10A Gene-Disease associations (from GenCC):

• episodic pain syndrome, familial, 2

  Inheritance: AD Classification: STRONG, LIMITED, NO_KNOWN Submitted by: Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
• sodium channelopathy-related small fiber neuropathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Brugada syndrome

  Inheritance: Unknown, AD Classification: LIMITED, NO_KNOWN Submitted by: Genomics England PanelApp, ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 3-38725824-T-C is Benign according to our data. Variant chr3-38725824-T-C is described in ClinVar as Benign. ClinVar VariationId is 1165939.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.836 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006514.4. 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
	SCN10A	NM_006514.4	MANE Select	c.3088-510A>G		intron	N/A	NP_006505.4	Q9Y5Y9
	SCN10A	NM_001293306.2		c.3088-513A>G		intron	N/A	NP_001280235.2	Q9Y5Y9
	SCN10A	NM_001293307.2		c.2794-510A>G		intron	N/A	NP_001280236.2	Q9Y5Y9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN10A	ENST00000449082.3	TSL:1 MANE Select	c.3088-510A>G		intron	N/A	ENSP00000390600.2	Q9Y5Y9
	SCN10A	ENST00000643924.1		c.3088-513A>G		intron	N/A	ENSP00000495595.1	A0A2R8Y6J6
	SCN10A	ENST00000655275.1		c.3115-513A>G		intron	N/A	ENSP00000499510.1	A0A590UJM0

Frequencies

GnomAD3 genomes AF: 0.668 AC: 101624 AN: 152082 Hom.: 34951 Cov.: 33

Gnomad AFR AF: 0.843

Gnomad AMI AF: 0.550

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.603

Gnomad EAS AF: 0.792

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.536

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.596

Gnomad OTH AF: 0.627

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

GnomAD4 genome AF: 0.669 AC: 101757 AN: 152200 Hom.: 35019 Cov.: 33 AF XY: 0.666 AC XY: 49537 AN XY: 74404

African (AFR) AF: 0.844 AC: 35058 AN: 41558

American (AMR) AF: 0.606 AC: 9272 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.603 AC: 2093 AN: 3472

East Asian (EAS) AF: 0.793 AC: 4095 AN: 5166

South Asian (SAS) AF: 0.636 AC: 3063 AN: 4814

European-Finnish (FIN) AF: 0.536 AC: 5667 AN: 10580

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.596 AC: 40505 AN: 67998

Other (OTH) AF: 0.629 AC: 1332 AN: 2116

Alfa AF: 0.624 Hom.: 87033

Bravo AF: 0.682

Asia WGS AF: 0.728 AC: 2531 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Brugada syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	17
DANN	Benign	0.82
PhyloP100		0.58
Mutation Taster		=100/0	polymorphism (auto)

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: rs6801957; hg19: chr3-38767315;