chr19-7556448-C-T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001166114.2(PNPLA6):c.3094-5C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00187 in 1,589,704 control chromosomes in the GnomAD database, including 39 homozygotes. 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 Likely benign (★★).
Frequency
Consequence
NM_001166114.2 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PNPLA6 | NM_001166114.2 | c.3094-5C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000600737.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PNPLA6 | ENST00000600737.6 | c.3094-5C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_001166114.2 | P3 |
Frequencies
GnomAD3 genomes AF: 0.00968 AC: 1472AN: 152056Hom.: 23 Cov.: 30
GnomAD3 exomes AF: 0.00251 AC: 630AN: 251474Hom.: 7 AF XY: 0.00185 AC XY: 252AN XY: 135910
GnomAD4 exome AF: 0.00105 AC: 1504AN: 1437530Hom.: 16 Cov.: 29 AF XY: 0.000925 AC XY: 663AN XY: 716498
GnomAD4 genome AF: 0.00968 AC: 1473AN: 152174Hom.: 23 Cov.: 30 AF XY: 0.00941 AC XY: 700AN XY: 74420
ClinVar
Submissions by phenotype
Hereditary spastic paraplegia 39 Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Dec 07, 2016 | - - |
Hereditary spastic paraplegia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Apr 08, 2021 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 24, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at