12-14973086-C-T
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_006205.3(PDE6H):c.-42C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,136 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 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
PDE6H
NM_006205.3 5_prime_UTR_premature_start_codon_gain
NM_006205.3 5_prime_UTR_premature_start_codon_gain
Scores
2
Splicing: ADA: 0.0006274
2
Clinical Significance
Conservation
PhyloP100: -0.928
Genes affected
PDE6H (HGNC:8790): (phosphodiesterase 6H) This gene encodes the inhibitory (or gamma) subunit of the cone-specific cGMP phosphodiesterase, which is a tetramer composed of two catalytic chains (alpha and beta), and two inhibitory chains (gamma). It is specifically expressed in the retina, and is involved in the transmission and amplification of the visual signal. Mutations in this gene are associated with retinal cone dystrophy type 3A (RCD3A). [provided by RefSeq, Mar 2010]
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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=-0.78).
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| PDE6H | NM_006205.3 | c.-42C>T | 5_prime_UTR_premature_start_codon_gain_variant | 1/4 | ENST00000266395.3 | NP_006196.1 | ||
| PDE6H | NM_006205.3 | c.-42C>T | splice_region_variant | 1/4 | ENST00000266395.3 | NP_006196.1 | ||
| PDE6H | NM_006205.3 | c.-42C>T | 5_prime_UTR_variant | 1/4 | ENST00000266395.3 | NP_006196.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| PDE6H | ENST00000266395 | c.-42C>T | 5_prime_UTR_premature_start_codon_gain_variant | 1/4 | 1 | NM_006205.3 | ENSP00000266395.2 | |||
| PDE6H | ENST00000266395.3 | c.-42C>T | splice_region_variant | 1/4 | 1 | NM_006205.3 | ENSP00000266395.2 | |||
| PDE6H | ENST00000266395 | c.-42C>T | 5_prime_UTR_variant | 1/4 | 1 | NM_006205.3 | ENSP00000266395.2 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152136Hom.: 0 Cov.: 32
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GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 20Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 14
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GnomAD4 genome 0.00000657 AC: 1AN: 152136Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74308
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Retinal cone dystrophy 3A Uncertain:1
| Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at