2-29073706-G-T
Variant summary
Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBS1_Supporting
The NM_001029883.3(PCARE):c.556C>A(p.Gln186Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000366 in 1,613,618 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001029883.3 missense
Scores
Clinical Significance
Conservation
Publications
- PCARE-related retinopathyInheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
- retinitis pigmentosa 54Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
- retinitis pigmentosaInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Likely_benign. The variant received -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PCARE | NM_001029883.3 | c.556C>A | p.Gln186Lys | missense_variant | Exon 1 of 2 | ENST00000331664.6 | NP_001025054.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PCARE | ENST00000331664.6 | c.556C>A | p.Gln186Lys | missense_variant | Exon 1 of 2 | 2 | NM_001029883.3 | ENSP00000332809.4 | ||
ENSG00000308575 | ENST00000835145.1 | n.224+4539G>T | intron_variant | Intron 2 of 2 | ||||||
ENSG00000308575 | ENST00000835146.1 | n.207+4539G>T | intron_variant | Intron 2 of 2 | ||||||
ENSG00000308575 | ENST00000835147.1 | n.171+4539G>T | intron_variant | Intron 2 of 2 |
Frequencies
GnomAD3 genomes AF: 0.000237 AC: 36AN: 151728Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.0000481 AC: 12AN: 249588 AF XY: 0.0000369 show subpopulations
GnomAD4 exome AF: 0.0000157 AC: 23AN: 1461890Hom.: 0 Cov.: 37 AF XY: 0.00000825 AC XY: 6AN XY: 727246 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.000237 AC: 36AN: 151728Hom.: 0 Cov.: 32 AF XY: 0.000243 AC XY: 18AN XY: 74104 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
not provided Uncertain:1
This sequence change replaces glutamine, which is neutral and polar, with lysine, which is basic and polar, at codon 186 of the PCARE protein (p.Gln186Lys). This variant is present in population databases (rs267606691, gnomAD 0.08%). This variant has not been reported in the literature in individuals affected with PCARE-related conditions. ClinVar contains an entry for this variant (Variation ID: 1423455). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. -
PCARE-related disorder Uncertain:1
The PCARE c.556C>A variant is predicted to result in the amino acid substitution p.Gln186Lys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.079% of alleles in individuals of African descent in gnomAD. Although we suspect this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at