chr2-166406105-C-T
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_002976.4(SCN7A):c.4524G>A(p.Lys1508=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000807 in 1,611,850 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 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000075 ( 0 hom. )
Consequence
SCN7A
NM_002976.4 synonymous
NM_002976.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.625
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 Likely_benign. Variant got -5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.61).
BP6
?
Variant 2-166406105-C-T is Benign according to our data. Variant chr2-166406105-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 750467.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.625 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN7A | NM_002976.4 | c.4524G>A | p.Lys1508= | synonymous_variant | 26/26 | ENST00000643258.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN7A | ENST00000643258.1 | c.4524G>A | p.Lys1508= | synonymous_variant | 26/26 | NM_002976.4 | P1 | ||
SCN7A | ENST00000441411.2 | c.4524G>A | p.Lys1508= | synonymous_variant | 25/25 | 1 | P1 | ||
SCN7A | ENST00000424326.5 | c.*2329G>A | 3_prime_UTR_variant, NMD_transcript_variant | 26/26 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 151888Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000816 AC: 2AN: 245092Hom.: 0 AF XY: 0.00000751 AC XY: 1AN XY: 133098
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GnomAD4 exome AF: 0.00000753 AC: 11AN: 1459962Hom.: 0 Cov.: 33 AF XY: 0.00000688 AC XY: 5AN XY: 726218
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jun 08, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at