Variant chr16-2971607-G-T 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.481G>T(p.Gly161Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PAQR4
NM_152341.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.25

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.481G>T	p.Gly161Cys	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.481G>T	p.Gly161Cys	missense_variant	3/3	1	NM_152341.5	P1	Q8N4S7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1451196

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722386

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2021

The c.481G>T (p.G161C) alteration is located in exon 3 (coding exon 3) of the PAQR4 gene. This alteration results from a G to T substitution at nucleotide position 481, causing the glycine (G) at amino acid position 161 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.060

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.014

T;.;.;T;.

Eigen

Uncertain

0.24

Eigen_PC

Benign

0.22

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.79

T;T;.;T;T

M_CAP

Uncertain

0.25

MetaRNN

Uncertain

0.53

D;D;D;D;D

MetaSVM

Benign

-0.77

MutationAssessor

Benign

0.90

L;.;.;.;.

MutationTaster

Benign

0.85

D;D;D;D;D;D

PrimateAI

Uncertain

0.74

PROVEAN

Benign

1.5

N;D;.;.;.

REVEL

Benign

0.19

Sift

Uncertain

0.019

D;D;.;.;.

Sift4G

Uncertain

0.039

D;T;D;D;D

Polyphen

0.97

D;D;.;.;.

Vest4

0.29

MutPred

0.58

Gain of catalytic residue at W162 (P = 0.0067);.;.;.;.;

MVP

0.46

MPC

0.56

ClinPred

0.96

GERP RS

4.4

Varity_R

0.16

gMVP

0.69

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over