rs59468016

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_006514.4(SCN10A):​c.2937C>T​(p.Gly979=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 1,611,748 control chromosomes in the GnomAD database, including 50,463 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3711 hom., cov: 32)
Exomes 𝑓: 0.25 ( 46752 hom. )

Consequence

SCN10A
NM_006514.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.358
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
Variant 3-38726756-G-A is Benign according to our data. Variant chr3-38726756-G-A is described in ClinVar as [Benign]. Clinvar id is 259994.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-38726756-G-A is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=0.358 with no splicing effect.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SCN10ANM_006514.4 linkuse as main transcriptc.2937C>T p.Gly979= synonymous_variant 17/28 ENST00000449082.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SCN10AENST00000449082.3 linkuse as main transcriptc.2937C>T p.Gly979= synonymous_variant 17/281 NM_006514.4 P4
SCN10AENST00000655275.1 linkuse as main transcriptc.2964C>T p.Gly988= synonymous_variant 17/28
SCN10AENST00000643924.1 linkuse as main transcriptc.2937C>T p.Gly979= synonymous_variant 16/27 A1

Frequencies

GnomAD3 genomes
AF:
0.195
AC:
29586
AN:
152034
Hom.:
3711
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0477
Gnomad AMI
AF:
0.330
Gnomad AMR
AF:
0.138
Gnomad ASJ
AF:
0.341
Gnomad EAS
AF:
0.403
Gnomad SAS
AF:
0.241
Gnomad FIN
AF:
0.270
Gnomad MID
AF:
0.203
Gnomad NFE
AF:
0.257
Gnomad OTH
AF:
0.193
GnomAD3 exomes
AF:
0.233
AC:
58345
AN:
250858
Hom.:
7747
AF XY:
0.239
AC XY:
32392
AN XY:
135540
show subpopulations
Gnomad AFR exome
AF:
0.0417
Gnomad AMR exome
AF:
0.108
Gnomad ASJ exome
AF:
0.335
Gnomad EAS exome
AF:
0.388
Gnomad SAS exome
AF:
0.229
Gnomad FIN exome
AF:
0.269
Gnomad NFE exome
AF:
0.257
Gnomad OTH exome
AF:
0.237
GnomAD4 exome
AF:
0.247
AC:
360494
AN:
1459596
Hom.:
46752
Cov.:
34
AF XY:
0.248
AC XY:
179590
AN XY:
725556
show subpopulations
Gnomad4 AFR exome
AF:
0.0376
Gnomad4 AMR exome
AF:
0.113
Gnomad4 ASJ exome
AF:
0.333
Gnomad4 EAS exome
AF:
0.425
Gnomad4 SAS exome
AF:
0.235
Gnomad4 FIN exome
AF:
0.270
Gnomad4 NFE exome
AF:
0.251
Gnomad4 OTH exome
AF:
0.236
GnomAD4 genome
AF:
0.194
AC:
29578
AN:
152152
Hom.:
3711
Cov.:
32
AF XY:
0.197
AC XY:
14622
AN XY:
74368
show subpopulations
Gnomad4 AFR
AF:
0.0476
Gnomad4 AMR
AF:
0.138
Gnomad4 ASJ
AF:
0.341
Gnomad4 EAS
AF:
0.403
Gnomad4 SAS
AF:
0.242
Gnomad4 FIN
AF:
0.270
Gnomad4 NFE
AF:
0.257
Gnomad4 OTH
AF:
0.191
Alfa
AF:
0.242
Hom.:
3284
Bravo
AF:
0.178
Asia WGS
AF:
0.263
AC:
917
AN:
3478
EpiCase
AF:
0.246
EpiControl
AF:
0.248

ClinVar

Significance: Benign
Submissions summary: Benign:9
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:6
Benign, criteria provided, single submitterclinical testingGeneDxSep 23, 2016This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Benign, criteria provided, single submitterclinical testingWomen's Health and Genetics/Laboratory Corporation of America, LabCorpApr 09, 2023- -
Benign, no assertion criteria providedclinical testingJoint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+-- -
Benign, no assertion criteria providedclinical testingClinical Genetics, Academic Medical Center-- -
Benign, criteria provided, single submitterclinical testingMolecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart InstituteJun 10, 2016- -
Brugada syndrome Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeFeb 01, 2024- -
Episodic pain syndrome, familial, 2 Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 15, 2021- -
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitterclinical testingAmbry GeneticsDec 21, 2018This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
CADD
Benign
1.1
DANN
Benign
0.50

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs59468016; hg19: chr3-38768247; COSMIC: COSV71860663; API