rs73969174
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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.5670T>Cā(p.Pro1890=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00125 in 1,614,038 control chromosomes in the GnomAD database, including 19 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 0.0069 ( 8 hom., cov: 32)
Exomes š: 0.00066 ( 11 hom. )
Consequence
SCN3A
NM_006922.4 synonymous
NM_006922.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.602
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=-0.61).
BP6
?
Variant 2-165090483-A-G is Benign according to our data. Variant chr2-165090483-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 412605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.602 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0069 (1050/152278) while in subpopulation AFR AF= 0.0243 (1009/41554). AF 95% confidence interval is 0.023. There are 8 homozygotes in gnomad4. There are 481 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 1050 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN3A | NM_006922.4 | c.5670T>C | p.Pro1890= | synonymous_variant | 28/28 | ENST00000283254.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN3A | ENST00000283254.12 | c.5670T>C | p.Pro1890= | synonymous_variant | 28/28 | 1 | NM_006922.4 | P1 | |
ENST00000638199.1 | n.1144-637A>G | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00689 AC: 1049AN: 152160Hom.: 8 Cov.: 32
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GnomAD3 exomes AF: 0.00175 AC: 440AN: 251072Hom.: 4 AF XY: 0.00116 AC XY: 158AN XY: 135658
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GnomAD4 exome AF: 0.000658 AC: 962AN: 1461760Hom.: 11 Cov.: 31 AF XY: 0.000536 AC XY: 390AN XY: 727174
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GnomAD4 genome ? AF: 0.00690 AC: 1050AN: 152278Hom.: 8 Cov.: 32 AF XY: 0.00646 AC XY: 481AN XY: 74448
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Sep 07, 2017 | - - |
SCN3A-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 02, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
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