3-38725210-C-T

Variant names:

• chr3-38725210-C-T
• rs6791171
• NM_006514.4:c.3192G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_006514.4(SCN10A):​c.3192G>A​(p.Thr1064Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 1,604,944 control chromosomes in the GnomAD database, including 17,413 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T1064T) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.15 (1926 hom., cov: 33)
  • Exomes 𝑓: 0.14 (15487 hom.)
• Consequence: SCN10A NM_006514.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -0.0480
• Publications: 9 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 3-38725210-C-T is Benign according to our data. Variant chr3-38725210-C-T is described in ClinVar as Benign. ClinVar VariationId is 259995.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.048 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.206 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.3192G>A	p.Thr1064Thr	synonymous	Exon 18 of 28	NP_006505.4	Q9Y5Y9
	SCN10A	NM_001293306.2		c.3189G>A	p.Thr1063Thr	synonymous	Exon 17 of 27	NP_001280235.2	Q9Y5Y9
	SCN10A	NM_001293307.2		c.2898G>A	p.Thr966Thr	synonymous	Exon 16 of 26	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.3192G>A	p.Thr1064Thr	synonymous	Exon 18 of 28	ENSP00000390600.2	Q9Y5Y9
	SCN10A	ENST00000643924.1		c.3189G>A	p.Thr1063Thr	synonymous	Exon 17 of 27	ENSP00000495595.1	A0A2R8Y6J6
	SCN10A	ENST00000655275.1		c.3216G>A	p.Thr1072Thr	synonymous	Exon 18 of 28	ENSP00000499510.1	A0A590UJM0

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22984 AN: 152092 Hom.: 1927 Cov.: 33

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.0914

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0839

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.120

GnomAD2 exomes AF: 0.121 AC: 30330 AN: 249642 AF XY: 0.119

Gnomad AFR exome AF: 0.204

Gnomad AMR exome AF: 0.123

Gnomad ASJ exome AF: 0.0873

Gnomad EAS exome AF: 0.000490

Gnomad FIN exome AF: 0.106

Gnomad NFE exome AF: 0.144

Gnomad OTH exome AF: 0.121

GnomAD4 exome AF: 0.141 AC: 205526 AN: 1452734 Hom.: 15487 Cov.: 35 AF XY: 0.139 AC XY: 100690 AN XY: 721916

African (AFR) AF: 0.207 AC: 6910 AN: 33328

American (AMR) AF: 0.121 AC: 5387 AN: 44388

Ashkenazi Jewish (ASJ) AF: 0.0869 AC: 2260 AN: 26008

East Asian (EAS) AF: 0.00121 AC: 48 AN: 39594

South Asian (SAS) AF: 0.0846 AC: 7211 AN: 85260

European-Finnish (FIN) AF: 0.109 AC: 5797 AN: 53262

Middle Eastern (MID) AF: 0.0657 AC: 375 AN: 5710

European-Non Finnish (NFE) AF: 0.154 AC: 169764 AN: 1105274

Other (OTH) AF: 0.130 AC: 7774 AN: 59910

GnomAD4 genome AF: 0.151 AC: 22995 AN: 152210 Hom.: 1926 Cov.: 33 AF XY: 0.146 AC XY: 10906 AN XY: 74456

African (AFR) AF: 0.210 AC: 8725 AN: 41512

American (AMR) AF: 0.131 AC: 2010 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0914 AC: 317 AN: 3468

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5176

South Asian (SAS) AF: 0.0835 AC: 403 AN: 4824

European-Finnish (FIN) AF: 0.106 AC: 1120 AN: 10608

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10048 AN: 68000

Other (OTH) AF: 0.118 AC: 248 AN: 2108

Alfa AF: 0.148 Hom.: 3630

Bravo AF: 0.156

Asia WGS AF: 0.0410 AC: 142 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	not specified (6)
-	-	1	Brugada syndrome (1)
-	-	1	Cardiovascular phenotype (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	5.4
DANN	Benign	0.26
PhyloP100		-0.048
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs6791171; hg19: chr3-38766701; COSMIC: COSV71860320;