chr3-38697724-A-G

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_006514.4(SCN10A):​c.5496T>C​(p.Thr1832Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000212 in 1,614,156 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00012 ( 1 hom. )

Consequence

SCN10A
NM_006514.4 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.239

Publications

0 publications found
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]
SCN10A Gene-Disease associations (from GenCC):
  • sodium channelopathy-related small fiber neuropathy
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • episodic pain syndrome, familial, 2
    Inheritance: AD Classification: LIMITED, NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae), Illumina, Ambry Genetics
  • Brugada syndrome
    Inheritance: Unknown Classification: LIMITED Submitted by: Genomics England PanelApp
  • Brugada syndrome 1
    Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.65).
BP6
Variant 3-38697724-A-G is Benign according to our data. Variant chr3-38697724-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 463267.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.239 with no splicing effect.
BS2
High AC in GnomAd4 at 173 AD,Unknown gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SCN10ANM_006514.4 linkc.5496T>C p.Thr1832Thr synonymous_variant Exon 28 of 28 ENST00000449082.3 NP_006505.4 Q9Y5Y9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SCN10AENST00000449082.3 linkc.5496T>C p.Thr1832Thr synonymous_variant Exon 28 of 28 1 NM_006514.4 ENSP00000390600.2 Q9Y5Y9
SCN10AENST00000643924.1 linkc.5493T>C p.Thr1831Thr synonymous_variant Exon 27 of 27 ENSP00000495595.1 A0A2R8Y6J6
SCN10AENST00000655275.1 linkc.5520T>C p.Thr1840Thr synonymous_variant Exon 28 of 28 ENSP00000499510.1 A0A590UJM0

Frequencies

GnomAD3 genomes
AF:
0.00114
AC:
173
AN:
152150
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00389
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000524
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00143
GnomAD2 exomes
AF:
0.000326
AC:
82
AN:
251246
AF XY:
0.000184
show subpopulations
Gnomad AFR exome
AF:
0.00474
Gnomad AMR exome
AF:
0.0000867
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.000116
AC:
169
AN:
1461888
Hom.:
1
Cov.:
32
AF XY:
0.000100
AC XY:
73
AN XY:
727244
show subpopulations
African (AFR)
AF:
0.00421
AC:
141
AN:
33480
American (AMR)
AF:
0.000201
AC:
9
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53420
Middle Eastern (MID)
AF:
0.000693
AC:
4
AN:
5768
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1112008
Other (OTH)
AF:
0.000248
AC:
15
AN:
60394
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.473
Heterozygous variant carriers
0
14
28
43
57
71
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
10
20
30
40
50
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.00114
AC:
173
AN:
152268
Hom.:
0
Cov.:
32
AF XY:
0.00120
AC XY:
89
AN XY:
74454
show subpopulations
African (AFR)
AF:
0.00387
AC:
161
AN:
41554
American (AMR)
AF:
0.000523
AC:
8
AN:
15298
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5168
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4812
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10628
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
292
European-Non Finnish (NFE)
AF:
0.0000147
AC:
1
AN:
68020
Other (OTH)
AF:
0.00142
AC:
3
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.496
Heterozygous variant carriers
0
9
18
28
37
46
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
4
8
12
16
20
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00144
Hom.:
0
Bravo
AF:
0.00141
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Apr 28, 2024
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Brugada syndrome Benign:1
Jan 29, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

not provided Benign:1
Oct 12, 2020
GeneDx
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Cardiovascular phenotype Benign:1
Apr 16, 2019
Ambry Genetics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This alteration is classified as likely 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
-0.65
CADD
Benign
0.54
DANN
Benign
0.70
PhyloP100
0.24
Mutation Taster
=100/0
polymorphism

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

Other links and lift over

dbSNP: rs112374164; hg19: chr3-38739215; COSMIC: COSV71862020; API