rs111389453
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_006922.4(SCN3A):āc.171T>Cā(p.Ala57=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000486 in 1,614,136 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.0026 ( 1 hom., cov: 32)
Exomes š: 0.00026 ( 3 hom. )
Consequence
SCN3A
NM_006922.4 synonymous
NM_006922.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.227
Genes affected
SCN3A (HGNC:10590): (sodium voltage-gated channel alpha subunit 3) Voltage-gated sodium channels are transmembrane glycoprotein complexes composed of a large alpha subunit with 24 transmembrane domains and one or more regulatory beta subunits. They are responsible for the generation and propagation of action potentials in neurons and muscle. This gene encodes one member of the sodium channel alpha subunit gene family, and is found in a cluster of five alpha subunit genes on chromosome 2. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
?
Variant 2-165176224-A-G is Benign according to our data. Variant chr2-165176224-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 196445.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-165176224-A-G is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=0.227 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00263 (401/152284) while in subpopulation AFR AF= 0.00895 (372/41574). AF 95% confidence interval is 0.0082. There are 1 homozygotes in gnomad4. There are 200 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 401 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN3A | NM_006922.4 | c.171T>C | p.Ala57= | synonymous_variant | 3/28 | ENST00000283254.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN3A | ENST00000283254.12 | c.171T>C | p.Ala57= | synonymous_variant | 3/28 | 1 | NM_006922.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00265 AC: 403AN: 152166Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000760 AC: 191AN: 251432Hom.: 0 AF XY: 0.000574 AC XY: 78AN XY: 135884
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GnomAD4 exome AF: 0.000262 AC: 383AN: 1461852Hom.: 3 Cov.: 31 AF XY: 0.000221 AC XY: 161AN XY: 727230
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GnomAD4 genome ? AF: 0.00263 AC: 401AN: 152284Hom.: 1 Cov.: 32 AF XY: 0.00269 AC XY: 200AN XY: 74476
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Nov 15, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Feb 10, 2015 | - - |
SCN3A-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 12, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Epilepsy, familial focal, with variable foci 4;C4693699:Developmental and epileptic encephalopathy, 62 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Aug 06, 2021 | - - |
Computational scores
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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