2-166406429-A-G
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1
The NM_002976.4(SCN7A):c.4200T>C(p.Tyr1400=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0914 in 1,612,920 control chromosomes in the GnomAD database, including 7,457 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.076 ( 529 hom., cov: 32)
Exomes 𝑓: 0.093 ( 6928 hom. )
Consequence
SCN7A
NM_002976.4 synonymous
NM_002976.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.854
Genes affected
SCN7A (HGNC:10594): (sodium voltage-gated channel alpha subunit 7) This gene encodes one of the many voltage-gated sodium channel proteins. For proper functioning of neurons and muscles during action potentials, voltage-gated sodium channels direct sodium ion diffusion for membrane depolarization. This sodium channel protein has some atypical characteristics; the similarity between the human and mouse proteins is lower compared to other orthologous sodium channel pairs. Also, the S4 segments, which sense voltage changes, have fewer positive charged residues that in other sodium channels; domain 4 has fewer arginine and lysine residues compared to other sodium channel proteins. Several alternatively spliced transcript variants exist, but the full-length natures of all of them remain unknown. [provided by RefSeq, Dec 2011]
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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=-0.61).
BP6
?
Variant 2-166406429-A-G is Benign according to our data. Variant chr2-166406429-A-G is described in ClinVar as [Benign]. Clinvar id is 3055922.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.854 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN7A | NM_002976.4 | c.4200T>C | p.Tyr1400= | synonymous_variant | 26/26 | ENST00000643258.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN7A | ENST00000643258.1 | c.4200T>C | p.Tyr1400= | synonymous_variant | 26/26 | NM_002976.4 | P1 | ||
SCN7A | ENST00000441411.2 | c.4200T>C | p.Tyr1400= | synonymous_variant | 25/25 | 1 | P1 | ||
SCN7A | ENST00000424326.5 | c.*2005T>C | 3_prime_UTR_variant, NMD_transcript_variant | 26/26 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0762 AC: 11575AN: 151982Hom.: 529 Cov.: 32
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GnomAD3 exomes AF: 0.0852 AC: 21100AN: 247784Hom.: 1093 AF XY: 0.0889 AC XY: 11950AN XY: 134388
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GnomAD4 exome AF: 0.0930 AC: 135802AN: 1460820Hom.: 6928 Cov.: 33 AF XY: 0.0943 AC XY: 68541AN XY: 726704
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GnomAD4 genome ? AF: 0.0761 AC: 11574AN: 152100Hom.: 529 Cov.: 32 AF XY: 0.0736 AC XY: 5476AN XY: 74362
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
SCN7A-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 26, 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). - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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Dann
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at