rs780673867
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_001349253.2(SCN11A):c.501_502insTCTTCACT(p.Gly168SerfsTer11) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000306 in 1,612,684 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. T167T) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001349253.2 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN11A | NM_001349253.2 | c.501_502insTCTTCACT | p.Gly168SerfsTer11 | frameshift_variant | 8/30 | ENST00000302328.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN11A | ENST00000302328.9 | c.501_502insTCTTCACT | p.Gly168SerfsTer11 | frameshift_variant | 8/30 | 5 | NM_001349253.2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000289 AC: 44AN: 152158Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000152 AC: 38AN: 250220Hom.: 0 AF XY: 0.000155 AC XY: 21AN XY: 135304
GnomAD4 exome AF: 0.000307 AC: 449AN: 1460526Hom.: 1 Cov.: 29 AF XY: 0.000295 AC XY: 214AN XY: 726592
GnomAD4 genome ? AF: 0.000289 AC: 44AN: 152158Hom.: 0 Cov.: 32 AF XY: 0.000229 AC XY: 17AN XY: 74330
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Nov 12, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Nov 08, 2023 | Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is not a known mechanism of disease; Has not been previously published as pathogenic or benign to our knowledge - |
Hereditary sensory and autonomic neuropathy type 7;C3809899:Familial episodic pain syndrome with predominantly lower limb involvement Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | May 03, 2022 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 13, 2023 | This sequence change creates a premature translational stop signal (p.Gly168Serfs*11) in the SCN11A gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in SCN11A cause disease. This variant is present in population databases (rs780673867, gnomAD 0.03%). This premature translational stop signal has been observed in individual(s) with clinical features of SCN11A-related conditions (Invitae). This premature translational stop signal has been observed in at least one individual who was not affected with SCN11A-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 474737). 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. - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 19, 2019 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at