Variant 16-2971677-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_152341.5(PAQR4):c.551G>A(p.Arg184His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000372 in 1,611,520 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

PAQR4
NM_152341.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.67

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 made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAQR4	NM_152341.5 linkuse as main transcript	c.551G>A	p.Arg184His	missense_variant	3/3	ENST00000318782.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAQR4	ENST00000318782.9 linkuse as main transcript	c.551G>A	p.Arg184His	missense_variant	3/3	1	NM_152341.5	P1	Q8N4S7-1

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

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

GnomAD3 exomes

AF:

0.0000767

AC:

AN:

247682

Hom.:

AF XY:

0.0000816

AC XY:

AN XY:

134814

show subpopulations

Gnomad AFR exome

AF:

0.0000638

Gnomad AMR exome

AF:

0.000435

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000481

Gnomad NFE exome

AF:

0.0000179

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000274

AC:

AN:

1459302

Hom.:

Cov.:

AF XY:

0.0000289

AC XY:

AN XY:

726020

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000358

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000189

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.000131

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00131

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

Bravo

AF:

0.000110

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.88

BayesDel_addAF

Benign

-0.014

BayesDel_noAF

Uncertain

0.070

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.21

T;.;.;T;.

Eigen

Uncertain

0.68

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.89

D;D;.;D;D

M_CAP

Benign

0.069

MetaRNN

Uncertain

0.74

D;D;D;D;D

MetaSVM

Benign

-0.71

MutationAssessor

Pathogenic

3.2

M;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Pathogenic

0.82

PROVEAN

Uncertain

-3.3

D;.;.;.;.

REVEL

Uncertain

0.36

Sift

Pathogenic

0.0

D;.;.;.;.

Sift4G

Uncertain

0.016

D;D;D;D;D

Polyphen

1.0

D;D;.;.;.

Vest4

0.75

MutPred

0.68

Loss of MoRF binding (P = 0.0087);.;.;.;.;

MVP

0.37

MPC

0.72

ClinPred

0.65

GERP RS

4.6

Varity_R

0.43

gMVP

0.91

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over