Genetic Variant PAQR9:p.Ala19Thr (chr3-142963282-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_198504.4(PAQR9):c.55G>A(p.Ala19Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000162 in 1,482,664 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000090 ( 0 hom. )

Consequence

PAQR9
NM_198504.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.337

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: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.041041344).

BP6

Variant 3-142963282-C-T is Benign according to our data. Variant chr3-142963282-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2409656.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 12 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.55G>A	p.Ala19Thr	missense	Exon 1 of 1	NP_940906.1	Q6ZVX9
PAQR9	NM_001375300.1		c.55G>A	p.Ala19Thr	missense	Exon 2 of 4	NP_001362229.1
PAQR9	NM_001375301.1		c.55G>A	p.Ala19Thr	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.55G>A	p.Ala19Thr	missense	Exon 1 of 1	ENSP00000341564.4	Q6ZVX9
PAQR9	ENST00000900185.1		c.55G>A	p.Ala19Thr	missense	Exon 2 of 2	ENSP00000570244.1
PAQR9	ENST00000900186.1		c.55G>A	p.Ala19Thr	missense	Exon 2 of 2	ENSP00000570245.1

Frequencies

GnomAD3 genomes

AF:

0.0000791

AC:

AN:

151774

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

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

GnomAD2 exomes

AF:

0.0000232

AC:

AN:

86246

AF XY:

0.0000213

show subpopulations

Gnomad AFR exome

AF:

0.000433

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000902

AC:

AN:

1330890

Hom.:

Cov.:

AF XY:

0.00000922

AC XY:

AN XY:

650956

show subpopulations

African (AFR)

AF:

0.000343

AC:

AN:

29182

American (AMR)

AF:

0.00

AC:

AN:

28608

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21642

East Asian (EAS)

AF:

0.00

AC:

AN:

33990

South Asian (SAS)

AF:

0.00

AC:

AN:

71014

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34682

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4374

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1052192

Other (OTH)

AF:

0.0000362

AC:

AN:

55206

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

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

AF:

0.0000791

AC:

AN:

151774

Hom.:

Cov.:

AF XY:

0.0000540

AC XY:

AN XY:

74114

show subpopulations

African (AFR)

AF:

0.000290

AC:

AN:

41390

American (AMR)

AF:

0.00

AC:

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5126

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10538

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67872

Other (OTH)

AF:

0.00

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

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

0.093

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.79

CADD

Benign

3.8

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.012

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.43

M_CAP

Benign

0.012

MetaRNN

Benign

0.041

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

-0.34

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.060

REVEL

Benign

0.0090

Sift

Benign

0.44

Sift4G

Benign

0.54

Polyphen

0.0

Vest4

0.056

MutPred

0.18

Loss of glycosylation at P18 (P = 0.0035)

MVP

0.043

MPC

1.1

ClinPred

0.013

GERP RS

-0.80

PromoterAI

-0.035

Neutral

(source)

Varity_R

0.042

gMVP

0.13

Mutation Taster

=97/3

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over