Variant 6-52403532-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_133367.5(PAQR8):c.319A>G(p.Thr107Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000706 in 1,613,988 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00047 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00073 ( 0 hom. )

Consequence

PAQR8
NM_133367.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0920

Variant links:

Genes affected

PAQR8 (HGNC:15708): (progestin and adipoQ receptor family member 8) Predicted to enable steroid binding activity and steroid hormone receptor activity. Predicted to be involved in response to steroid hormone. Located in Golgi apparatus and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

PAQR8 links:

EFHC1 (HGNC:16406): (EF-hand domain containing 1) This gene encodes an EF-hand-containing calcium binding protein. The encoded protein likely plays a role in calcium homeostasis. Mutations in this gene have been associated with susceptibility to juvenile myoclonic epilepsy and juvenile absence epilepsy. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2010]

EFHC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.010501504).

BP6

Variant 6-52403532-A-G is Benign according to our data. Variant chr6-52403532-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2398745.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAQR8	NM_133367.5 linkuse as main transcript	c.319A>G	p.Thr107Ala	missense_variant	2/2	ENST00000442253.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAQR8	ENST00000442253.3 linkuse as main transcript	c.319A>G	p.Thr107Ala	missense_variant	2/2	1	NM_133367.5	P1

Frequencies

GnomAD3 genomes

AF:

0.000473

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.000941

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000390

AC:

AN:

251272

Hom.:

AF XY:

0.000368

AC XY:

AN XY:

135836

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000173

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000792

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000731

AC:

1068

AN:

1461698

Hom.:

Cov.:

AF XY:

0.000696

AC XY:

506

AN XY:

727164

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000751

Gnomad4 NFE exome

AF:

0.000914

Gnomad4 OTH exome

AF:

0.000464

GnomAD4 genome

AF:

0.000466

AC:

AN:

152290

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000926

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000655

Hom.:

Bravo

AF:

0.000408

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.000436

AC:

EpiCase

AF:

0.000654

EpiControl

AF:

0.000533

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 01, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.027

DANN

Benign

0.41

DEOGEN2

Benign

0.045

.;T;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.056

LIST_S2

Benign

0.39

T;.;T

M_CAP

Benign

0.0070

MetaRNN

Benign

0.011

T;T;T

MetaSVM

Benign

-0.93

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

0.88

N;N;N

REVEL

Benign

0.034

Sift

Benign

0.72

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

.;B;B

Vest4

0.013

MVP

0.19

MPC

0.37

ClinPred

0.016

GERP RS

-3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.016

gMVP

0.068

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