3-38846704-T-C
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_001349253.2(SCN11A):āc.5366A>Gā(p.His1789Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,613,678 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 Uncertain significance (ā ā ).
Frequency
Consequence
NM_001349253.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SCN11A | NM_001349253.2 | c.5366A>G | p.His1789Arg | missense_variant | Exon 30 of 30 | ENST00000302328.9 | NP_001336182.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152124Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250926Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135606
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461554Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5AN XY: 727066
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152124Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74300
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.5366A>G (p.H1789R) alteration is located in exon 26 (coding exon 26) of the SCN11A gene. This alteration results from a A to G substitution at nucleotide position 5366, causing the histidine (H) at amino acid position 1789 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Hereditary sensory and autonomic neuropathy type 7;C3809899:Familial episodic pain syndrome with predominantly lower limb involvement Uncertain:1
This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 1789 of the SCN11A protein (p.His1789Arg). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with SCN11A-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at