rs200972952
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3PP5
The NM_001365536.1(SCN9A):c.377+5C>T variant causes a splice donor 5th base, intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000339 in 1,476,702 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001365536.1 splice_donor_5th_base, intron
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN9A | NM_001365536.1 | c.377+5C>T | splice_donor_5th_base_variant, intron_variant | ENST00000642356.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN9A | ENST00000642356.2 | c.377+5C>T | splice_donor_5th_base_variant, intron_variant | NM_001365536.1 | P1 | ||||
SCN1A-AS1 | ENST00000651574.1 | n.1977+10822G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152024Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000827 AC: 2AN: 241898Hom.: 0 AF XY: 0.00000764 AC XY: 1AN XY: 130916
GnomAD4 exome AF: 0.00000302 AC: 4AN: 1324678Hom.: 0 Cov.: 19 AF XY: 0.00000450 AC XY: 3AN XY: 666200
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152024Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74250
ClinVar
Submissions by phenotype
Pain insensitivity Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Centre for Mendelian Genomics, University Medical Centre Ljubljana | Apr 21, 2015 | - - |
Generalized epilepsy with febrile seizures plus, type 7;C2752089:Neuropathy, hereditary sensory and autonomic, type 2A Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 16, 2020 | This variant is not present in population databases (ExAC no frequency). 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. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing, but this prediction has not been confirmed by published transcriptional studies. This variant has been observed in individual(s) with insensitivity to pain (PMID: 28914264, 30795902). ClinVar contains an entry for this variant (Variation ID: 374103). This sequence change falls in intron 3 of the SCN9A gene. It does not directly change the encoded amino acid sequence of the SCN9A protein, but it affects a nucleotide within the consensus splice site of the intron. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at