20-63981306-C-T
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Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2
The NM_012469.4(PRPF6):c.61C>T(p.Leu21=) variant causes a synonymous change. The variant allele was found at a frequency of 0.0000817 in 1,602,606 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000079 ( 1 hom. )
Consequence
PRPF6
NM_012469.4 synonymous
NM_012469.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.77
Genes affected
PRPF6 (HGNC:15860): (pre-mRNA processing factor 6) The protein encoded by this gene appears to be involved in pre-mRNA splicing, possibly acting as a bridging factor between U5 and U4/U6 snRNPs in formation of the spliceosome. The encoded protein also can bind androgen receptor, providing a link between transcriptional activation and splicing. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -7 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.24).
BP6
Variant 20-63981306-C-T is Benign according to our data. Variant chr20-63981306-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 898313.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=1}.
BS2
High AC in GnomAd4 at 16 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
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PRPF6 | NM_012469.4 | c.61C>T | p.Leu21= | synonymous_variant | 1/21 | ENST00000266079.5 | |
PRPF6 | XM_006723769.4 | c.61C>T | p.Leu21= | synonymous_variant | 1/20 | ||
PRPF6 | XR_007067448.1 | n.175C>T | non_coding_transcript_exon_variant | 1/20 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRPF6 | ENST00000266079.5 | c.61C>T | p.Leu21= | synonymous_variant | 1/21 | 1 | NM_012469.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000105 AC: 16AN: 152176Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000139 AC: 31AN: 222780Hom.: 0 AF XY: 0.000131 AC XY: 16AN XY: 121732
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GnomAD4 exome AF: 0.0000793 AC: 115AN: 1450430Hom.: 1 Cov.: 31 AF XY: 0.0000860 AC XY: 62AN XY: 720604
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GnomAD4 genome AF: 0.000105 AC: 16AN: 152176Hom.: 0 Cov.: 33 AF XY: 0.0000942 AC XY: 7AN XY: 74344
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Retinitis pigmentosa Uncertain:1
Uncertain significance, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Aug 30, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at