Genetic Variant SCN10A:c.*123C>T (chr3-38697226-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006514.4(SCN10A):c.*123C>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 0.443 in 1,470,942 control chromosomes in the GnomAD database, including 147,134 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.44 ( 14628 hom., cov: 32)

Exomes 𝑓: 0.44 ( 132506 hom. )

Consequence

SCN10A
NM_006514.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.649

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 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 3-38697226-G-A is Benign according to our data. Variant chr3-38697226-G-A is described in ClinVar as [Benign]. Clinvar id is 1259657.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN10A	NM_006514.4 link	c.*123C>T		3_prime_UTR_variant	Exon 28 of 28	ENST00000449082.3	NP_006505.4	Q9Y5Y9

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SCN10A	ENST00000449082 link	c.*123C>T	3_prime_UTR_variant	Exon 28 of 28	1	NM_006514.4	ENSP00000390600.2	Q9Y5Y9
SCN10A	ENST00000655275 link	c.*123C>T	3_prime_UTR_variant	Exon 28 of 28			ENSP00000499510.1	A0A590UJM0
SCN10A	ENST00000643924.1 link	c.*123C>T	downstream_gene_variant				ENSP00000495595.1	A0A2R8Y6J6

Frequencies

GnomAD3 genomes

AF:

0.437

AC:

66303

AN:

151894

Hom.:

14636

Cov.:

show subpopulations

Gnomad AFR

AF:

0.449

Gnomad AMI

AF:

0.482

Gnomad AMR

AF:

0.402

Gnomad ASJ

AF:

0.419

Gnomad EAS

AF:

0.138

Gnomad SAS

AF:

0.412

Gnomad FIN

AF:

0.477

Gnomad MID

AF:

0.519

Gnomad NFE

AF:

0.454

Gnomad OTH

AF:

0.455

GnomAD4 exome

AF:

0.444

AC:

585843

AN:

1318930

Hom.:

132506

Cov.:

AF XY:

0.445

AC XY:

287556

AN XY:

646802

show subpopulations

Gnomad4 AFR exome

AF:

0.458

AC:

13585

AN:

29690

Gnomad4 AMR exome

AF:

0.375

AC:

11160

AN:

29742

Gnomad4 ASJ exome

AF:

0.417

AC:

8312

AN:

19942

Gnomad4 EAS exome

AF:

0.128

AC:

4919

AN:

38500

Gnomad4 SAS exome

AF:

0.434

AC:

29527

AN:

68062

Gnomad4 FIN exome

AF:

0.465

AC:

18491

AN:

39746

Gnomad4 NFE exome

AF:

0.458

AC:

474325

AN:

1034762

Gnomad4 Remaining exome

AF:

0.433

AC:

23758

AN:

54810

Heterozygous variant carriers

15831

31662

47493

63324

79155

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

14480

28960

43440

57920

72400

<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:

0.436

AC:

66308

AN:

152012

Hom.:

14628

Cov.:

AF XY:

0.432

AC XY:

32106

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.448

AC:

0.448241

AN:

0.448241

Gnomad4 AMR

AF:

0.402

AC:

0.40212

AN:

0.40212

Gnomad4 ASJ

AF:

0.419

AC:

0.418638

AN:

0.418638

Gnomad4 EAS

AF:

0.138

AC:

0.137804

AN:

0.137804

Gnomad4 SAS

AF:

0.411

AC:

0.410982

AN:

0.410982

Gnomad4 FIN

AF:

0.477

AC:

0.477083

AN:

0.477083

Gnomad4 NFE

AF:

0.454

AC:

0.454136

AN:

0.454136

Gnomad4 OTH

AF:

0.452

AC:

0.451659

AN:

0.451659

Heterozygous variant carriers

1903

3806

5709

7612

9515

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

618

1236

1854

2472

3090

<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:

0.445

Hom.:

50167

Bravo

AF:

0.430

Asia WGS

AF:

0.297

AC:

1036

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 19, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.77

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

Publications

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over