Variant chr12-41188849-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001164595.2(PDZRN4):c.394G>A(p.Gly132Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000841 in 1,261,908 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00042 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00090 ( 0 hom. )

Consequence

PDZRN4
NM_001164595.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.682

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.040729135).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDZRN4	NM_001164595.2 linkuse as main transcript	c.394G>A	p.Gly132Ser	missense_variant	1/10	ENST00000402685.7	NP_001158067.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDZRN4	ENST00000402685.7 linkuse as main transcript	c.394G>A	p.Gly132Ser	missense_variant	1/10	2	NM_001164595.2	ENSP00000384197	P1	Q6ZMN7-1

Frequencies

GnomAD3 genomes

AF:

0.000423

AC:

AN:

148946

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000170

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000134

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00165

Gnomad FIN

AF:

0.000214

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.000613

Gnomad OTH

AF:

0.000976

GnomAD4 exome

AF:

0.000897

AC:

998

AN:

1112854

Hom.:

Cov.:

AF XY:

0.000931

AC XY:

494

AN XY:

530482

show subpopulations

Gnomad4 AFR exome

AF:

0.0000444

Gnomad4 AMR exome

AF:

0.000374

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000666

Gnomad4 SAS exome

AF:

0.00229

Gnomad4 FIN exome

AF:

0.000204

Gnomad4 NFE exome

AF:

0.000922

Gnomad4 OTH exome

AF:

0.000716

GnomAD4 genome

AF:

0.000423

AC:

AN:

149054

Hom.:

Cov.:

AF XY:

0.000385

AC XY:

AN XY:

72708

show subpopulations

Gnomad4 AFR

AF:

0.000170

Gnomad4 AMR

AF:

0.000133

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.000214

Gnomad4 NFE

AF:

0.000613

Gnomad4 OTH

AF:

0.000965

Alfa

AF:

0.000212

Hom.:

Bravo

AF:

0.000389

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

Jun 11, 2021

The c.394G>A (p.G132S) alteration is located in exon 1 (coding exon 1) of the PDZRN4 gene. This alteration results from a G to A substitution at nucleotide position 394, causing the glycine (G) at amino acid position 132 to be replaced by a serine (S). 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

0.096

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.0093

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.44

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.041

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.34

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.43

REVEL

Benign

0.027

Sift

Benign

0.17

Sift4G

Benign

0.15

Vest4

0.10

MVP

0.52

MPC

0.89

ClinPred

0.055

GERP RS

0.53

Varity_R

0.039

gMVP

0.19

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