rs146624492
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2
The NM_006922.4(SCN3A):āc.5889T>Cā(p.Ser1963=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000417 in 1,612,058 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.00032 ( 0 hom., cov: 32)
Exomes š: 0.00043 ( 0 hom. )
Consequence
SCN3A
NM_006922.4 synonymous
NM_006922.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.223
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 -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
?
Variant 2-165090264-A-G is Benign according to our data. Variant chr2-165090264-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 288551.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.
BP7
?
Synonymous conserved (PhyloP=0.223 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000315 (48/152172) while in subpopulation SAS AF= 0.000828 (4/4830). AF 95% confidence interval is 0.000392. There are 0 homozygotes in gnomad4. There are 23 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 48 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN3A | NM_006922.4 | c.5889T>C | p.Ser1963= | synonymous_variant | 28/28 | ENST00000283254.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN3A | ENST00000283254.12 | c.5889T>C | p.Ser1963= | synonymous_variant | 28/28 | 1 | NM_006922.4 | P1 | |
ENST00000638199.1 | n.1144-856A>G | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000315 AC: 48AN: 152172Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000335 AC: 83AN: 247782Hom.: 0 AF XY: 0.000366 AC XY: 49AN XY: 133830
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GnomAD4 exome AF: 0.000428 AC: 625AN: 1459886Hom.: 0 Cov.: 31 AF XY: 0.000460 AC XY: 334AN XY: 726062
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GnomAD4 genome ? AF: 0.000315 AC: 48AN: 152172Hom.: 0 Cov.: 32 AF XY: 0.000309 AC XY: 23AN XY: 74350
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Sep 01, 2023 | SCN3A: BP4, BP7 - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 19, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 17, 2024 | - - |
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