Genetic Variant PDZD8:p.Glu983Glu (chr10-117283784-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_173791.5(PDZD8):c.2949G>A(p.Glu983Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00764 in 1,614,156 control chromosomes in the GnomAD database, including 65 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0053 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0079 ( 60 hom. )

Consequence

PDZD8
NM_173791.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.622

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

intellectual developmental disorder with autism and dysmorphic facies
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

PDZD8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 10-117283784-C-T is Benign according to our data. Variant chr10-117283784-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3770459.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.622 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDZD8	NM_173791.5 link	c.2949G>A	p.Glu983Glu	synonymous_variant	Exon 5 of 5	ENST00000334464.7	NP_776152.1	Q8NEN9
PDZD8	XM_005269518.5 link	c.2826G>A	p.Glu942Glu	synonymous_variant	Exon 4 of 4		XP_005269575.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDZD8	ENST00000334464.7 link	c.2949G>A	p.Glu983Glu	synonymous_variant	Exon 5 of 5	1	NM_173791.5	ENSP00000334642.5		Q8NEN9

Frequencies

GnomAD3 genomes

AF:

0.00528

AC:

804

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00162

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00321

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.00387

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00914

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00544

AC:

1367

AN:

251404

AF XY:

0.00546

show subpopulations

Gnomad AFR exome

AF:

0.00166

Gnomad AMR exome

AF:

0.00147

Gnomad ASJ exome

AF:

0.00347

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00389

Gnomad NFE exome

AF:

0.00942

Gnomad OTH exome

AF:

0.00375

GnomAD4 exome

AF:

0.00789

AC:

11527

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00773

AC XY:

5625

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.00114

AC:

AN:

33480

American (AMR)

AF:

0.00165

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00318

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00270

AC:

233

AN:

86258

European-Finnish (FIN)

AF:

0.00431

AC:

230

AN:

53416

Middle Eastern (MID)

AF:

0.00416

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00947

AC:

10530

AN:

1112008

Other (OTH)

AF:

0.00522

AC:

315

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

795

1590

2384

3179

3974

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00527

AC:

803

AN:

152270

Hom.:

Cov.:

AF XY:

0.00449

AC XY:

334

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.00161

AC:

AN:

41548

American (AMR)

AF:

0.00320

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00228

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00387

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00913

AC:

621

AN:

68026

Other (OTH)

AF:

0.00284

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

124

166

207

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00696

Hom.:

Bravo

AF:

0.00500

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00927

EpiControl

AF:

0.00960

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

PDZD8: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

5.4

(source)

DANN

Benign

0.89

PhyloP100

0.62

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

chr10-117283784-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over