chr3-38871515-T-C
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001349253.2(SCN11A):āc.3689A>Gā(p.Asn1230Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000484 in 1,613,028 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N1230D) has been classified as Uncertain significance.
Frequency
Consequence
NM_001349253.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN11A | NM_001349253.2 | c.3689A>G | p.Asn1230Ser | missense_variant | 25/30 | ENST00000302328.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN11A | ENST00000302328.9 | c.3689A>G | p.Asn1230Ser | missense_variant | 25/30 | 5 | NM_001349253.2 | A2 |
Frequencies
GnomAD3 genomes AF: 0.000105 AC: 16AN: 152168Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000200 AC: 5AN: 249920Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 135014
GnomAD4 exome AF: 0.0000424 AC: 62AN: 1460860Hom.: 0 Cov.: 31 AF XY: 0.0000427 AC XY: 31AN XY: 726694
GnomAD4 genome AF: 0.000105 AC: 16AN: 152168Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74316
ClinVar
Submissions by phenotype
Hereditary sensory and autonomic neuropathy type 7;C3809899:Familial episodic pain syndrome with predominantly lower limb involvement Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 23, 2022 | ClinVar contains an entry for this variant (Variation ID: 541552). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SCN11A protein function. This variant has not been reported in the literature in individuals affected with SCN11A-related conditions. This variant is present in population databases (rs765543089, gnomAD 0.01%). This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 1230 of the SCN11A protein (p.Asn1230Ser). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at