rs6599250
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_006514.4(SCN10A):c.1868-9A>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.621 in 1,609,664 control chromosomes in the GnomAD database, including 316,134 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.70 ( 38358 hom., cov: 32)
Exomes 𝑓: 0.61 ( 277776 hom. )
Consequence
SCN10A
NM_006514.4 splice_polypyrimidine_tract, intron
NM_006514.4 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.00006857
2
Clinical Significance
Conservation
PhyloP100: -0.669
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
?
Variant 3-38742538-T-C is Benign according to our data. Variant chr3-38742538-T-C is described in ClinVar as [Benign]. Clinvar id is 259993.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-38742538-T-C is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN10A | NM_006514.4 | c.1868-9A>G | splice_polypyrimidine_tract_variant, intron_variant | ENST00000449082.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN10A | ENST00000449082.3 | c.1868-9A>G | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_006514.4 | P4 | |||
SCN10A | ENST00000643924.1 | c.1868-9A>G | splice_polypyrimidine_tract_variant, intron_variant | A1 | |||||
SCN10A | ENST00000655275.1 | c.1895-9A>G | splice_polypyrimidine_tract_variant, intron_variant |
Frequencies
GnomAD3 genomes ? AF: 0.696 AC: 105735AN: 151962Hom.: 38285 Cov.: 32
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GnomAD3 exomes AF: 0.649 AC: 161550AN: 248812Hom.: 53874 AF XY: 0.641 AC XY: 86427AN XY: 134896
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GnomAD4 exome AF: 0.614 AC: 894283AN: 1457584Hom.: 277776 Cov.: 32 AF XY: 0.613 AC XY: 444436AN XY: 725452
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GnomAD4 genome ? AF: 0.696 AC: 105874AN: 152080Hom.: 38358 Cov.: 32 AF XY: 0.694 AC XY: 51596AN XY: 74332
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ClinVar
Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:5
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 06, 2016 | This 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, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Apr 04, 2023 | - - |
Episodic pain syndrome, familial, 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Brugada syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at