19-54115679-G-A
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2
The ENST00000419967.5(PRPF31):c.-127G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000104 in 346,250 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00013 ( 0 hom. )
Consequence
PRPF31
ENST00000419967.5 5_prime_UTR
ENST00000419967.5 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.335
Genes affected
PRPF31 (HGNC:15446): (pre-mRNA processing factor 31) This gene encodes a component of the spliceosome complex and is one of several retinitis pigmentosa-causing genes. When the gene product is added to the spliceosome complex, activation occurs.[provided by RefSeq, Jan 2009]
TFPT (HGNC:13630): (TCF3 fusion partner) Predicted to enable DNA binding activity and protein kinase binding activity. Involved in apoptotic signaling pathway. Located in nucleoplasm. Part of Ino80 complex. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0000722 (11/152322) while in subpopulation SAS AF= 0.00207 (10/4826). AF 95% confidence interval is 0.00112. There are 0 homozygotes in gnomad4. There are 7 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
BS2
High AC in GnomAd4 at 11 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TFPT | NM_013342.4 | upstream_gene_variant | ENST00000391759.6 | NP_037474.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PRPF31 | ENST00000419967.5 | c.-127G>A | 5_prime_UTR_variant | 1/13 | 5 | ENSP00000405166 | ||||
TFPT | ENST00000391759.6 | upstream_gene_variant | 1 | NM_013342.4 | ENSP00000375639 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152204Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.000129 AC: 25AN: 193928Hom.: 0 Cov.: 0 AF XY: 0.000235 AC XY: 23AN XY: 97718
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GnomAD4 genome AF: 0.0000722 AC: 11AN: 152322Hom.: 0 Cov.: 33 AF XY: 0.0000940 AC XY: 7AN XY: 74476
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Retinitis Pigmentosa, Dominant Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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Name
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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