14-67727476-G-A
Variant names:
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_152443.3(RDH12):c.658+286G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000068 in 147,044 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.0000068 ( 0 hom., cov: 28)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
RDH12
NM_152443.3 intron
NM_152443.3 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.298
Genes affected
RDH12 (HGNC:19977): (retinol dehydrogenase 12) The protein encoded by this gene is an NADPH-dependent retinal reductase whose highest activity is toward 9-cis and all-trans-retinol. The encoded enzyme also plays a role in the metabolism of short-chain aldehydes but does not exhibit steroid dehydrogenase activity. Defects in this gene are a cause of Leber congenital amaurosis type 13 and Retinitis Pigmentosa 53. [provided by RefSeq, Sep 2015]
GPHN (HGNC:15465): (gephyrin) This gene encodes a neuronal assembly protein that anchors inhibitory neurotransmitter receptors to the postsynaptic cytoskeleton via high affinity binding to a receptor subunit domain and tubulin dimers. In nonneuronal tissues, the encoded protein is also required for molybdenum cofactor biosynthesis. Mutations in this gene may be associated with the neurological condition hyperplexia and also lead to molybdenum cofactor deficiency. Numerous alternatively spliced transcript variants encoding different isoforms have been described; however, the full-length nature of all transcript variants is not currently known. [provided by RefSeq, Jul 2008]
ZFYVE26 (HGNC:20761): (zinc finger FYVE-type containing 26) This gene encodes a protein which contains a FYVE zinc finger binding domain. The presence of this domain is thought to target these proteins to membrane lipids through interaction with phospholipids in the membrane. Mutations in this gene are associated with autosomal recessive spastic paraplegia-15. [provided by RefSeq, Oct 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.93).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RDH12 | NM_152443.3 | c.658+286G>A | intron_variant | Intron 7 of 8 | ENST00000551171.6 | NP_689656.2 | ||
GPHN | XM_047430879.1 | c.1313-7719G>A | intron_variant | Intron 14 of 14 | XP_047286835.1 | |||
RDH12 | XM_047430965.1 | c.658+286G>A | intron_variant | Intron 7 of 8 | XP_047286921.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RDH12 | ENST00000551171.6 | c.658+286G>A | intron_variant | Intron 7 of 8 | 1 | NM_152443.3 | ENSP00000449079.1 | |||
RDH12 | ENST00000267502.3 | c.658+286G>A | intron_variant | Intron 6 of 7 | 5 | ENSP00000267502.3 | ||||
ZFYVE26 | ENST00000394455.6 | n.4032C>T | non_coding_transcript_exon_variant | Exon 15 of 15 | 2 | |||||
RDH12 | ENST00000552873.1 | n.27+286G>A | intron_variant | Intron 1 of 1 | 5 |
Frequencies
GnomAD3 genomes AF: 0.00000680 AC: 1AN: 147044Hom.: 0 Cov.: 28
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GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 154708Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 83982
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GnomAD4 genome AF: 0.00000680 AC: 1AN: 147044Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0AN XY: 71458
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ClinVar
Not reported inComputational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at