Variant X-153803873-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001303512.2(PDZD4):c.1808G>A(p.Gly603Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000027 in 1,186,025 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., 6 hem., cov: 25)

Exomes 𝑓: 0.000011 ( 0 hom. 3 hem. )

Consequence

PDZD4
NM_001303512.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.96

Variant links:

Genes affected

PDZD4 (HGNC:21167): (PDZ domain containing 4) Predicted to be located in cell cortex. [provided by Alliance of Genome Resources, Apr 2022]

PDZD4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.067736626).

BS2

High Hemizygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDZD4	NM_001303512.2 linkuse as main transcript	c.1808G>A	p.Gly603Asp	missense_variant	8/8	ENST00000393758.7	NP_001290441.1	Q76G19Q17RL8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PDZD4	ENST00000393758.7 linkuse as main transcript	c.1808G>A	p.Gly603Asp	missense_variant	8/8	1	NM_001303512.2	ENSP00000377355.3	Q17RL8
PDZD4	ENST00000164640.8 linkuse as main transcript	c.1790G>A	p.Gly597Asp	missense_variant	8/8	1		ENSP00000164640.4	Q76G19-1
PDZD4	ENST00000544474.5 linkuse as main transcript	c.1463G>A	p.Gly488Asp	missense_variant	6/6	1		ENSP00000442033.1	Q76G19-2

Frequencies

GnomAD3 genomes

AF:

0.000176

AC:

AN:

113776

Hom.:

Cov.:

AF XY:

0.000167

AC XY:

AN XY:

35924

show subpopulations

Gnomad AFR

AF:

0.000605

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000187

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000439

AC:

AN:

136663

Hom.:

AF XY:

0.0000718

AC XY:

AN XY:

41793

show subpopulations

Gnomad AFR exome

AF:

0.000515

Gnomad AMR exome

AF:

0.0000414

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000112

AC:

AN:

1072249

Hom.:

Cov.:

AF XY:

0.00000864

AC XY:

AN XY:

347031

show subpopulations

Gnomad4 AFR exome

AF:

0.000426

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000120

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000176

AC:

AN:

113776

Hom.:

Cov.:

AF XY:

0.000167

AC XY:

AN XY:

35924

show subpopulations

Gnomad4 AFR

AF:

0.000605

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000187

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000285

Hom.:

Bravo

AF:

0.000155

ExAC

AF:

0.00000865

AC:

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

Mar 01, 2024

The c.1790G>A (p.G597D) alteration is located in exon 8 (coding exon 8) of the PDZD4 gene. This alteration results from a G to A substitution at nucleotide position 1790, causing the glycine (G) at amino acid position 597 to be replaced by an aspartic acid (D). 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

0.12

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.18

T;.;T

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.77

T;T;T

M_CAP

Benign

0.074

MetaRNN

Benign

0.068

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;.;.

MutationTaster

Benign

0.92

D;D;D

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-1.3

N;N;.

REVEL

Benign

0.11

Sift

Benign

0.059

T;T;.

Sift4G

Benign

0.18

T;T;T

Polyphen

0.0

B;.;B

Vest4

0.20

MVP

0.62

MPC

1.1

ClinPred

0.033

GERP RS

3.9

Varity_R

0.17

gMVP

0.47

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