Variant rs363294 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_173791.5(PDZD8):c.2690G>A(p.Arg897Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0505 in 1,614,066 control chromosomes in the GnomAD database, including 2,526 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict 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 0.039 ( 164 hom., cov: 32)

Exomes 𝑓: 0.052 ( 2362 hom. )

Consequence

PDZD8
NM_173791.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.870

Variant links:

Genes affected

PDZD8 (HGNC:26974): (PDZ domain containing 8) Predicted to enable lipid binding activity and metal ion binding activity. Involved in several processes, including mitochondrial calcium ion homeostasis; mitochondrion-endoplasmic reticulum membrane tethering; and regulation of cell morphogenesis. Located in endoplasmic reticulum membrane and mitochondria-associated endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

PDZD8 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0013818741).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0752 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDZD8	NM_173791.5 linkuse as main transcript	c.2690G>A	p.Arg897Gln	missense_variant	5/5	ENST00000334464.7	NP_776152.1
PDZD8	XM_005269518.5 linkuse as main transcript	c.2567G>A	p.Arg856Gln	missense_variant	4/4		XP_005269575.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDZD8	ENST00000334464.7 linkuse as main transcript	c.2690G>A	p.Arg897Gln	missense_variant	5/5	1	NM_173791.5	ENSP00000334642	P1

Frequencies

GnomAD3 genomes

AF:

0.0391

AC:

5945

AN:

152124

Hom.:

161

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00934

Gnomad AMI

AF:

0.00659

Gnomad AMR

AF:

0.0266

Gnomad ASJ

AF:

0.112

Gnomad EAS

AF:

0.00963

Gnomad SAS

AF:

0.0816

Gnomad FIN

AF:

0.0349

Gnomad MID

AF:

0.0446

Gnomad NFE

AF:

0.0564

Gnomad OTH

AF:

0.0439

GnomAD3 exomes

AF:

0.0491

AC:

12320

AN:

251140

Hom.:

437

AF XY:

0.0526

AC XY:

7142

AN XY:

135732

show subpopulations

Gnomad AFR exome

AF:

0.00812

Gnomad AMR exome

AF:

0.0228

Gnomad ASJ exome

AF:

0.109

Gnomad EAS exome

AF:

0.00850

Gnomad SAS exome

AF:

0.0843

Gnomad FIN exome

AF:

0.0344

Gnomad NFE exome

AF:

0.0573

Gnomad OTH exome

AF:

0.0522

GnomAD4 exome

AF:

0.0517

AC:

75593

AN:

1461824

Hom.:

2362

Cov.:

AF XY:

0.0535

AC XY:

38939

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.00944

Gnomad4 AMR exome

AF:

0.0236

Gnomad4 ASJ exome

AF:

0.109

Gnomad4 EAS exome

AF:

0.0116

Gnomad4 SAS exome

AF:

0.0830

Gnomad4 FIN exome

AF:

0.0342

Gnomad4 NFE exome

AF:

0.0526

Gnomad4 OTH exome

AF:

0.0507

GnomAD4 genome

AF:

0.0392

AC:

5962

AN:

152242

Hom.:

164

Cov.:

AF XY:

0.0383

AC XY:

2849

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.00936

Gnomad4 AMR

AF:

0.0265

Gnomad4 ASJ

AF:

0.112

Gnomad4 EAS

AF:

0.00965

Gnomad4 SAS

AF:

0.0818

Gnomad4 FIN

AF:

0.0349

Gnomad4 NFE

AF:

0.0564

Gnomad4 OTH

AF:

0.0501

Alfa

AF:

0.0571

Hom.:

794

Bravo

AF:

0.0360

TwinsUK

AF:

0.0583

AC:

216

ALSPAC

AF:

0.0519

AC:

200

ESP6500AA

AF:

0.00908

AC:

ESP6500EA

AF:

0.0574

AC:

494

ExAC

AF:

0.0496

AC:

6025

Asia WGS

AF:

0.0480

AC:

168

AN:

3478

EpiCase

AF:

0.0631

EpiControl

AF:

0.0610

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.013

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.77

MetaRNN

Benign

0.0014

MetaSVM

Benign

-0.85

MutationAssessor

Benign

0.81

MutationTaster

Benign

1.0

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.65

REVEL

Benign

0.10

Sift

Benign

0.048

Sift4G

Benign

0.089

Polyphen

0.0090

Vest4

0.021

MPC

0.25

ClinPred

0.0065

GERP RS

1.7

Varity_R

0.061

gMVP

0.55

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