Variant 12-41552737-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001164595.2(PDZRN4):c.1285G>A(p.Gly429Ser) variant causes a missense change. The variant allele was found at a frequency of 0.163 in 1,611,684 control chromosomes in the GnomAD database, including 22,491 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.18 ( 2585 hom., cov: 32)

Exomes 𝑓: 0.16 ( 19906 hom. )

Consequence

PDZRN4
NM_001164595.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.72

Variant links:

Genes affected

PDZRN4 (HGNC:30552): (PDZ domain containing ring finger 4) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

PDZRN4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017770231).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDZRN4	NM_001164595.2 linkuse as main transcript	c.1285G>A	p.Gly429Ser	missense_variant	6/10	ENST00000402685.7
PDZRN4	NM_013377.4 linkuse as main transcript	c.511G>A	p.Gly171Ser	missense_variant	4/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDZRN4	ENST00000402685.7 linkuse as main transcript	c.1285G>A	p.Gly429Ser	missense_variant	6/10	2	NM_001164595.2	P1	Q6ZMN7-1

Frequencies

GnomAD3 genomes

AF:

0.181

AC:

27443

AN:

151850

Hom.:

2584

Cov.:

show subpopulations

Gnomad AFR

AF:

0.241

Gnomad AMI

AF:

0.105

Gnomad AMR

AF:

0.121

Gnomad ASJ

AF:

0.183

Gnomad EAS

AF:

0.0978

Gnomad SAS

AF:

0.173

Gnomad FIN

AF:

0.189

Gnomad MID

AF:

0.212

Gnomad NFE

AF:

0.164

Gnomad OTH

AF:

0.175

GnomAD3 exomes

AF:

0.158

AC:

39614

AN:

250912

Hom.:

3522

AF XY:

0.161

AC XY:

21879

AN XY:

135580

show subpopulations

Gnomad AFR exome

AF:

0.245

Gnomad AMR exome

AF:

0.0770

Gnomad ASJ exome

AF:

0.179

Gnomad EAS exome

AF:

0.0942

Gnomad SAS exome

AF:

0.176

Gnomad FIN exome

AF:

0.186

Gnomad NFE exome

AF:

0.168

Gnomad OTH exome

AF:

0.163

GnomAD4 exome

AF:

0.161

AC:

234743

AN:

1459714

Hom.:

19906

Cov.:

AF XY:

0.162

AC XY:

117904

AN XY:

726268

show subpopulations

Gnomad4 AFR exome

AF:

0.241

Gnomad4 AMR exome

AF:

0.0837

Gnomad4 ASJ exome

AF:

0.176

Gnomad4 EAS exome

AF:

0.107

Gnomad4 SAS exome

AF:

0.179

Gnomad4 FIN exome

AF:

0.189

Gnomad4 NFE exome

AF:

0.160

Gnomad4 OTH exome

AF:

0.163

GnomAD4 genome

AF:

0.181

AC:

27452

AN:

151970

Hom.:

2585

Cov.:

AF XY:

0.179

AC XY:

13305

AN XY:

74258

show subpopulations

Gnomad4 AFR

AF:

0.241

Gnomad4 AMR

AF:

0.121

Gnomad4 ASJ

AF:

0.183

Gnomad4 EAS

AF:

0.0974

Gnomad4 SAS

AF:

0.172

Gnomad4 FIN

AF:

0.189

Gnomad4 NFE

AF:

0.164

Gnomad4 OTH

AF:

0.173

Alfa

AF:

0.164

Hom.:

5436

Bravo

AF:

0.176

TwinsUK

AF:

0.152

AC:

562

ALSPAC

AF:

0.157

AC:

605

ESP6500AA

AF:

0.239

AC:

1055

ESP6500EA

AF:

0.161

AC:

1387

ExAC

AF:

0.165

AC:

20013

Asia WGS

AF:

0.141

AC:

495

AN:

3478

EpiCase

AF:

0.163

EpiControl

AF:

0.160

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.050

T;.;.;.

Eigen

Pathogenic

0.72

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.87

D;D;D;D

MetaRNN

Benign

0.0018

T;T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.6

L;.;.;.

MutationTaster

Benign

0.0000021

P;P;P

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-4.3

D;.;D;D

REVEL

Uncertain

0.29

Sift

Benign

0.10

T;.;D;D

Sift4G

Benign

0.083

T;.;D;D

Polyphen

1.0

D;.;D;D

Vest4

0.27

MPC

0.41

ClinPred

0.019

GERP RS

5.0

Varity_R

0.58

gMVP

0.68

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