Genetic Variant PAQR4:p.Gly37Ser (chr16-2969783-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_152341.5(PAQR4):c.109G>A(p.Gly37Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000549 in 1,602,548 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 0.00025 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

PAQR4
NM_152341.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.15

Publications

0 publications found

Variant links:

Genes affected

PAQR4 (HGNC:26386): (progestin and adipoQ receptor family member 4) Predicted to enable signaling receptor activity. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

PAQR4 links:

PKMYT1 (HGNC:29650): (protein kinase, membrane associated tyrosine/threonine 1) This gene encodes a member of the serine/threonine protein kinase family. The encoded protein is a membrane-associated kinase that negatively regulates the G2/M transition of the cell cycle by phosphorylating and inactivating cyclin-dependent kinase 1. The activity of the encoded protein is regulated by polo-like kinase 1. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, May 2012]

PKMYT1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.15181738).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152341.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PAQR4	NM_152341.5	MANE Select	c.109G>A	p.Gly37Ser	missense	Exon 1 of 3	NP_689554.2
PAQR4	NM_001284511.2		c.109G>A	p.Gly37Ser	missense	Exon 1 of 3	NP_001271440.1	Q8N4S7-2
PAQR4	NM_001324118.2		c.109G>A	p.Gly37Ser	missense	Exon 1 of 4	NP_001311047.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PAQR4	ENST00000318782.9	TSL:1 MANE Select	c.109G>A	p.Gly37Ser	missense	Exon 1 of 3	ENSP00000321804.8	Q8N4S7-1
PAQR4	ENST00000293978.12	TSL:2	c.109G>A	p.Gly37Ser	missense	Exon 1 of 3	ENSP00000293978.8	Q8N4S7-2
PAQR4	ENST00000896898.1		c.109G>A	p.Gly37Ser	missense	Exon 1 of 3	ENSP00000566957.1

Frequencies

GnomAD3 genomes

AF:

0.000256

AC:

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000845

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000463

AC:

AN:

216144

AF XY:

0.0000415

show subpopulations

Gnomad AFR exome

AF:

0.000430

Gnomad AMR exome

AF:

0.000122

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:

0.0000345

AC:

AN:

1450338

Hom.:

Cov.:

AF XY:

0.0000388

AC XY:

AN XY:

721102

show subpopulations

African (AFR)

AF:

0.00103

AC:

AN:

32918

American (AMR)

AF:

0.000138

AC:

AN:

43616

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25956

East Asian (EAS)

AF:

0.00

AC:

AN:

38826

South Asian (SAS)

AF:

0.0000351

AC:

AN:

85466

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50214

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5716

European-Non Finnish (NFE)

AF:

0.00000181

AC:

AN:

1107830

Other (OTH)

AF:

0.0000836

AC:

AN:

59796

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

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:

0.000250

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.000842

AC:

AN:

41558

American (AMR)

AF:

0.000131

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5152

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67962

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

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:

0.0000282

Hom.:

Bravo

AF:

0.000321

ExAC

AF:

0.0000611

AC:

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

0.12

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.010

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.022

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.92

M_CAP

Uncertain

0.24

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

PhyloP100

7.2

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.60

REVEL

Benign

0.064

Sift

Benign

0.27

Sift4G

Benign

0.59

Polyphen

0.84

Vest4

0.30

MVP

0.25

MPC

0.19

ClinPred

0.12

GERP RS

4.5

PromoterAI

0.019

Neutral

(source)

Varity_R

0.16

gMVP

0.55

Mutation Taster

=67/33

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