Genetic Variant NM_152341.5:c.212C>T (chr16-2971202-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_152341.5(PAQR4):c.212C>T(p.Pro71Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,076 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

PAQR4
NM_152341.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.50

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: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.212C>T	p.Pro71Leu	missense	Exon 2 of 3	NP_689554.2
PAQR4	NM_001284513.2		c.11C>T	p.Pro4Leu	missense	Exon 2 of 3	NP_001271442.1	I3L1A2
PAQR4	NM_001324118.2		c.212C>T	p.Pro71Leu	missense	Exon 2 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.212C>T	p.Pro71Leu	missense	Exon 2 of 3	ENSP00000321804.8	Q8N4S7-1
PAQR4	ENST00000574988.1	TSL:2	c.11C>T	p.Pro4Leu	missense	Exon 1 of 2	ENSP00000458683.1	I3L1A2
PAQR4	ENST00000576565.1	TSL:2	c.11C>T	p.Pro4Leu	missense	Exon 2 of 3	ENSP00000460326.1	I3L1A2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000320

AC:

AN:

250262

AF XY:

0.0000295

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000435

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461076

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726852

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.000126

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52646

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111988

Other (OTH)

AF:

0.00

AC:

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

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:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000247

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

Pathogenic

0.69

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.13

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.83

M_CAP

Benign

0.068

MetaRNN

Uncertain

0.70

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.1

PhyloP100

4.5

PrimateAI

Uncertain

0.73

PROVEAN

Pathogenic

-5.9

REVEL

Uncertain

0.29

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.019

Polyphen

0.99

Vest4

0.86

MutPred

0.79

Loss of loop (P = 0.1242)

MVP

0.22

MPC

0.63

ClinPred

0.61

GERP RS

4.7

PromoterAI

-0.018

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.65

gMVP

0.78

Mutation Taster

=30/70

disease causing

(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

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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