1-211477453-C-CA
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BS1_Supporting
The NM_001164688.2(RD3):c.*1582_*1583insT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00335 in 104,156 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0034 ( 0 hom., cov: 26)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
RD3
NM_001164688.2 3_prime_UTR
NM_001164688.2 3_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.934
Genes affected
RD3 (HGNC:19689): (RD3 regulator of GUCY2D) This gene encodes a retinal protein that is associated with promyelocytic leukemia-gene product (PML) bodies in the nucleus. Mutations in this gene cause Leber congenital amaurosis type 12, a disease that results in retinal degeneration. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00335 (349/104156) while in subpopulation AFR AF= 0.00544 (168/30904). AF 95% confidence interval is 0.00477. There are 0 homozygotes in gnomad4. There are 169 alleles in male gnomad4 subpopulation. Median coverage is 26. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| RD3 | NM_001164688.2 | c.*1582_*1583insT | 3_prime_UTR_variant | 3/3 | ENST00000680073.1 | NP_001158160.1 | ||
| RD3 | NM_183059.3 | c.*1582_*1583insT | 3_prime_UTR_variant | 3/3 | NP_898882.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| RD3 | ENST00000680073.1 | c.*1582_*1583insT | 3_prime_UTR_variant | 3/3 | NM_001164688.2 | ENSP00000505312 | P1 | |||
| RD3 | ENST00000367002.5 | c.*1582_*1583insT | 3_prime_UTR_variant | 3/3 | 1 | ENSP00000355969 | P1 | |||
| RD3 | ENST00000484910.1 | n.2138_2139insT | non_coding_transcript_exon_variant | 2/2 | 1 |
Frequencies
GnomAD3 genomes 0.00334 AC: 348AN: 104100Hom.: 0 Cov.: 26
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GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 2Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 2
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GnomAD4 genome 0.00335 AC: 349AN: 104156Hom.: 0 Cov.: 26 AF XY: 0.00341 AC XY: 169AN XY: 49558
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Leber congenital amaurosis Uncertain:1
| Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at