6-52404270-G-T
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_133367.5(PAQR8):c.1057G>T(p.Asp353Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000017 in 1,586,480 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: 33)
Exomes 𝑓: 0.000018 ( 0 hom. )
Consequence
PAQR8
NM_133367.5 missense
NM_133367.5 missense
Scores
1
5
12
Clinical Significance
Conservation
PhyloP100: 7.27
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 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.20417118).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PAQR8 | NM_133367.5 | c.1057G>T | p.Asp353Tyr | missense_variant | 2/2 | ENST00000442253.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PAQR8 | ENST00000442253.3 | c.1057G>T | p.Asp353Tyr | missense_variant | 2/2 | 1 | NM_133367.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152242Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000339 AC: 8AN: 236172Hom.: 0 AF XY: 0.0000312 AC XY: 4AN XY: 128084
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GnomAD4 exome AF: 0.0000181 AC: 26AN: 1434120Hom.: 0 Cov.: 33 AF XY: 0.0000212 AC XY: 15AN XY: 707760
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GnomAD4 genome AF: 0.00000656 AC: 1AN: 152360Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74506
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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 05, 2023 | The c.1057G>T (p.D353Y) alteration is located in exon 2 (coding exon 1) of the PAQR8 gene. This alteration results from a G to T substitution at nucleotide position 1057, causing the aspartic acid (D) at amino acid position 353 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
.;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D
REVEL
Benign
Sift
Benign
D;D
Sift4G
Uncertain
D;D
Polyphen
P;P
Vest4
MutPred
Loss of solvent accessibility (P = 0.0352);Loss of solvent accessibility (P = 0.0352);
MVP
MPC
ClinPred
T
GERP RS
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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