Genetic Variant PAQR9:p.Gly9Ser (chr3-142963312-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_198504.4(PAQR9):c.25G>A(p.Gly9Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000661 in 151,396 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Consequence

PAQR9
NM_198504.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.116

Variant links:

Genes affected

PAQR9 (HGNC:30131): (progestin and adipoQ receptor family member 9) Predicted to enable signaling receptor activity. Predicted to be located in plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

PAQR9 links:

PAQR9-AS1 (HGNC:50861): (PAQR9 antisense RNA 1)

PAQR9-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.043291688).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAQR9	NM_198504.4 link	c.25G>A	p.Gly9Ser	missense_variant	Exon 1 of 1	ENST00000340634.6	NP_940906.1	Q6ZVX9
PAQR9	NM_001375300.1 link	c.25G>A	p.Gly9Ser	missense_variant	Exon 2 of 4		NP_001362229.1
PAQR9	NM_001375301.1 link	c.25G>A	p.Gly9Ser	missense_variant	Exon 2 of 4		NP_001362230.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAQR9	ENST00000340634.6 link	c.25G>A	p.Gly9Ser	missense_variant	Exon 1 of 1	6	NM_198504.4	ENSP00000341564.4		Q6ZVX9

Frequencies

GnomAD3 genomes

AF:

0.00000661

AC:

AN:

151288

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000661

AC:

AN:

151396

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74010

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 07, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.25G>A (p.G9S) alteration is located in exon 1 (coding exon 1) of the PAQR9 gene. This alteration results from a G to A substitution at nucleotide position 25, causing the glycine (G) at amino acid position 9 to be replaced by a serine (S). 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

0.12

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.75

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.012

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.52

M_CAP

Benign

0.059

MetaRNN

Benign

0.043

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.20

REVEL

Benign

0.034

Sift

Benign

0.25

Sift4G

Benign

0.28

Polyphen

0.0

Vest4

0.077

MutPred

0.16

Loss of glycosylation at K13 (P = 0.0192);

MVP

0.082

MPC

1.1

ClinPred

0.22

GERP RS

0.87

Varity_R

0.092

gMVP

0.32

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over