chr6-52403656-A-G
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_133367.5(PAQR8):āc.443A>Gā(p.Tyr148Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000165 in 1,614,020 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 (ā ).
Frequency
Genomes: š 0.00020 ( 0 hom., cov: 33)
Exomes š: 0.00016 ( 0 hom. )
Consequence
PAQR8
NM_133367.5 missense
NM_133367.5 missense
Scores
11
5
2
Clinical Significance
Conservation
PhyloP100: 9.32
Genes affected
PAQR8 (HGNC:15708): (progestin and adipoQ receptor family member 8) Predicted to enable steroid binding activity and steroid hormone receptor activity. Predicted to be involved in response to steroid hormone. Located in Golgi apparatus and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]
EFHC1 (HGNC:16406): (EF-hand domain containing 1) This gene encodes an EF-hand-containing calcium binding protein. The encoded protein likely plays a role in calcium homeostasis. Mutations in this gene have been associated with susceptibility to juvenile myoclonic epilepsy and juvenile absence epilepsy. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.885
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PAQR8 | NM_133367.5 | c.443A>G | p.Tyr148Cys | missense_variant | 2/2 | ENST00000442253.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PAQR8 | ENST00000442253.3 | c.443A>G | p.Tyr148Cys | missense_variant | 2/2 | 1 | NM_133367.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000204 AC: 31AN: 152180Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000915 AC: 23AN: 251448Hom.: 0 AF XY: 0.0000957 AC XY: 13AN XY: 135902
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GnomAD4 exome AF: 0.000161 AC: 235AN: 1461840Hom.: 0 Cov.: 34 AF XY: 0.000135 AC XY: 98AN XY: 727222
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GnomAD4 genome AF: 0.000204 AC: 31AN: 152180Hom.: 0 Cov.: 33 AF XY: 0.000175 AC XY: 13AN XY: 74340
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 21, 2023 | The c.443A>G (p.Y148C) alteration is located in exon 2 (coding exon 1) of the PAQR8 gene. This alteration results from a A to G substitution at nucleotide position 443, causing the tyrosine (Y) at amino acid position 148 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
.;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
T
PROVEAN
Pathogenic
D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;D
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
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