Genetic Variant PAQR9:p.Ser108Asn (chr3-142963014-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_ModerateBS2

The NM_198504.4(PAQR9):c.323G>A(p.Ser108Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

PAQR9
NM_198504.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.08

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08809495).

BS2

High AC in GnomAdExome4 at 5 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198504.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PAQR9	NM_198504.4	MANE Select	c.323G>A	p.Ser108Asn	missense	Exon 1 of 1	NP_940906.1	Q6ZVX9
PAQR9	NM_001375300.1		c.323G>A	p.Ser108Asn	missense	Exon 2 of 4	NP_001362229.1
PAQR9	NM_001375301.1		c.323G>A	p.Ser108Asn	missense	Exon 2 of 4	NP_001362230.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PAQR9	ENST00000340634.6	TSL:6 MANE Select	c.323G>A	p.Ser108Asn	missense	Exon 1 of 1	ENSP00000341564.4	Q6ZVX9
PAQR9	ENST00000900185.1		c.323G>A	p.Ser108Asn	missense	Exon 2 of 2	ENSP00000570244.1
PAQR9	ENST00000900186.1		c.323G>A	p.Ser108Asn	missense	Exon 2 of 2	ENSP00000570245.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000160

AC:

AN:

250756

AF XY:

0.0000147

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461846

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727228

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.0000447

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111990

Other (OTH)

AF:

0.0000166

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.016

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.31

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.48

M_CAP

Benign

0.0076

MetaRNN

Benign

0.088

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.73

PhyloP100

3.1

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.40

REVEL

Benign

0.050

Sift

Benign

0.21

Sift4G

Benign

0.36

Polyphen

0.013

Vest4

0.098

MutPred

0.41

Loss of glycosylation at S108 (P = 0.0057)

MVP

0.15

MPC

1.4

ClinPred

0.13

GERP RS

3.8

PromoterAI

0.013

Neutral

(source)

Varity_R

0.15

gMVP

0.42

Mutation Taster

=91/9

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over