15-69389737-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_017705.4(PAQR5):​c.469G>A​(p.Val157Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000684 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

PAQR5
NM_017705.4 missense

Scores

2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.49
Variant links:
Genes affected
PAQR5 (HGNC:29645): (progestin and adipoQ receptor family member 5) Predicted to enable signaling receptor activity. Predicted to be involved in oogenesis. Predicted to be located in plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.37088716).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PAQR5NM_017705.4 linkuse as main transcriptc.469G>A p.Val157Ile missense_variant 6/9 ENST00000395407.7 NP_060175.3 Q9NXK6A0A024R607

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PAQR5ENST00000395407.7 linkuse as main transcriptc.469G>A p.Val157Ile missense_variant 6/91 NM_017705.4 ENSP00000378803.2 Q9NXK6

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251446
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135890
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:
0.00
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000684
AC:
10
AN:
1461858
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
727240
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:
0.00
Gnomad4 FIN exome
AF:
0.0000374
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.0000662
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.0000151

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 GeneticsDec 04, 2024The c.469G>A (p.V157I) alteration is located in exon 6 (coding exon 4) of the PAQR5 gene. This alteration results from a G to A substitution at nucleotide position 469, causing the valine (V) at amino acid position 157 to be replaced by an isoleucine (I). 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
0.090
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.029
T;.;T;T
Eigen
Benign
-0.014
Eigen_PC
Benign
0.023
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Benign
0.68
.;T;.;T
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.37
T;T;T;T
MetaSVM
Benign
-1.1
T
PrimateAI
Benign
0.39
T
PROVEAN
Benign
-0.47
N;N;N;N
REVEL
Benign
0.13
Sift
Benign
0.25
T;T;T;T
Sift4G
Benign
0.25
T;T;T;T
Polyphen
0.36
B;.;B;B
Vest4
0.37
MutPred
0.67
Gain of catalytic residue at L162 (P = 0.0336);.;Gain of catalytic residue at L162 (P = 0.0336);Gain of catalytic residue at L162 (P = 0.0336);
MVP
0.27
MPC
0.53
ClinPred
0.59
D
GERP RS
3.7
Varity_R
0.067
gMVP
0.29

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: rs1016734627; hg19: chr15-69682076; COSMIC: COSV61819311; COSMIC: COSV61819311; API