chr6-52403733-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_133367.5(PAQR8):​c.520C>T​(p.Arg174Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000169 in 1,614,212 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 0.00014 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

PAQR8
NM_133367.5 missense

Scores

4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.39
Variant links:
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]

Genome browser will be placed here

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=0.16911691).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PAQR8NM_133367.5 linkuse as main transcriptc.520C>T p.Arg174Trp missense_variant 2/2 ENST00000442253.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PAQR8ENST00000442253.3 linkuse as main transcriptc.520C>T p.Arg174Trp missense_variant 2/21 NM_133367.5 P1

Frequencies

GnomAD3 genomes
AF:
0.000145
AC:
22
AN:
152202
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.000188
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000235
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000215
AC:
54
AN:
251444
Hom.:
0
AF XY:
0.000250
AC XY:
34
AN XY:
135894
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000229
Gnomad FIN exome
AF:
0.000185
Gnomad NFE exome
AF:
0.000369
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000172
AC:
251
AN:
1461892
Hom.:
0
Cov.:
34
AF XY:
0.000179
AC XY:
130
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000174
Gnomad4 FIN exome
AF:
0.000243
Gnomad4 NFE exome
AF:
0.000183
Gnomad4 OTH exome
AF:
0.000281
GnomAD4 genome
AF:
0.000144
AC:
22
AN:
152320
Hom.:
0
Cov.:
33
AF XY:
0.000148
AC XY:
11
AN XY:
74496
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.000188
Gnomad4 NFE
AF:
0.000235
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000289
Hom.:
0
Bravo
AF:
0.000140
ExAC
AF:
0.000206
AC:
25
EpiCase
AF:
0.000545
EpiControl
AF:
0.000533

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 submitterclinical testingAmbry GeneticsJul 20, 2022The c.520C>T (p.R174W) alteration is located in exon 2 (coding exon 1) of the PAQR8 gene. This alteration results from a C to T substitution at nucleotide position 520, causing the arginine (R) at amino acid position 174 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.41
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.084
T;T
Eigen
Uncertain
0.35
Eigen_PC
Uncertain
0.33
FATHMM_MKL
Benign
0.52
D
LIST_S2
Uncertain
0.91
.;D
M_CAP
Benign
0.0088
T
MetaRNN
Benign
0.17
T;T
MetaSVM
Benign
-1.1
T
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.40
T
PROVEAN
Benign
-1.8
N;N
REVEL
Benign
0.13
Sift
Benign
0.061
T;T
Sift4G
Benign
0.12
T;T
Polyphen
0.98
D;D
Vest4
0.29
MVP
0.68
MPC
0.94
ClinPred
0.10
T
GERP RS
5.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.074
gMVP
0.36

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs201072442; hg19: chr6-52268531; API