chr12-14978107-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3
The NM_006205.3(PDE6H):c.95G>A(p.Arg32His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,613,544 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000096 ( 0 hom. )
Consequence
PDE6H
NM_006205.3 missense
NM_006205.3 missense
Scores
8
6
4
Clinical Significance
Conservation
PhyloP100: 9.92
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 Uncertain_significance. Variant got 1 ACMG points.
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.827
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PDE6H | NM_006205.3 | c.95G>A | p.Arg32His | missense_variant | 2/4 | ENST00000266395.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PDE6H | ENST00000266395.3 | c.95G>A | p.Arg32His | missense_variant | 2/4 | 1 | NM_006205.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152074Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251138Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135744
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GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461470Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 727024
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GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152074Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3AN XY: 74296
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 12, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 1350820). This variant has not been reported in the literature in individuals affected with PDE6H-related conditions. This variant is present in population databases (rs752287362, gnomAD 0.01%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 32 of the PDE6H protein (p.Arg32His). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Benign
T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Benign
T
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Gain of catalytic residue at K37 (P = 0.0074);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
Splicing
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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