rs141828577
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_006514.4(SCN10A):c.4584C>T(p.Phe1528=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000465 in 1,614,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000092 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000042 ( 0 hom. )
Consequence
SCN10A
NM_006514.4 synonymous
NM_006514.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.825
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 -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.39).
BP6
?
Variant 3-38701912-G-A is Benign according to our data. Variant chr3-38701912-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 509580.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.825 with no splicing effect.
BS2
?
High AC in GnomAd4 at 14 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN10A | NM_006514.4 | c.4584C>T | p.Phe1528= | synonymous_variant | 27/28 | ENST00000449082.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN10A | ENST00000449082.3 | c.4584C>T | p.Phe1528= | synonymous_variant | 27/28 | 1 | NM_006514.4 | P4 | |
SCN10A | ENST00000655275.1 | c.4608C>T | p.Phe1536= | synonymous_variant | 27/28 | ||||
SCN10A | ENST00000643924.1 | c.4581C>T | p.Phe1527= | synonymous_variant | 26/27 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000920 AC: 14AN: 152222Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000677 AC: 17AN: 251138Hom.: 0 AF XY: 0.0000737 AC XY: 10AN XY: 135696
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GnomAD4 exome AF: 0.0000417 AC: 61AN: 1461784Hom.: 0 Cov.: 31 AF XY: 0.0000578 AC XY: 42AN XY: 727188
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GnomAD4 genome ? AF: 0.0000920 AC: 14AN: 152222Hom.: 0 Cov.: 33 AF XY: 0.0000941 AC XY: 7AN XY: 74362
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 12, 2017 | 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. - |
Brugada syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 11, 2019 | 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
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at