1-160128855-T-G
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_000702.4(ATP1A2):c.1216+5T>G variant causes a splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000297 in 1,613,708 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000702.4 splice_donor_5th_base, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATP1A2 | NM_000702.4 | c.1216+5T>G | splice_donor_5th_base_variant, intron_variant | ENST00000361216.8 | |||
ATP1A2 | XM_047421286.1 | c.325+5T>G | splice_donor_5th_base_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATP1A2 | ENST00000361216.8 | c.1216+5T>G | splice_donor_5th_base_variant, intron_variant | 1 | NM_000702.4 | P1 | |||
ATP1A2 | ENST00000392233.7 | c.1216+5T>G | splice_donor_5th_base_variant, intron_variant | 5 | |||||
ATP1A2 | ENST00000447527.1 | c.348+5T>G | splice_donor_5th_base_variant, intron_variant | 2 | |||||
ATP1A2 | ENST00000472488.5 | n.1319+5T>G | splice_donor_5th_base_variant, intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 151822Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000756 AC: 19AN: 251322Hom.: 0 AF XY: 0.0000736 AC XY: 10AN XY: 135844
GnomAD4 exome AF: 0.0000301 AC: 44AN: 1461886Hom.: 0 Cov.: 34 AF XY: 0.0000344 AC XY: 25AN XY: 727242
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 151822Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74148
ClinVar
Submissions by phenotype
Familial hemiplegic migraine Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 24, 2023 | 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. Variants that disrupt 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. ClinVar contains an entry for this variant (Variation ID: 204870). This variant has not been reported in the literature in individuals affected with ATP1A2-related conditions. This variant is present in population databases (rs780155641, gnomAD 0.08%). This sequence change falls in intron 9 of the ATP1A2 gene. It does not directly change the encoded amino acid sequence of the ATP1A2 protein. It affects a nucleotide within the consensus splice site. - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 18, 2014 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at