Genetic Variant PDZD4:p.Gly603Asp (chrX-153803873-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 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

Publications

0 publications found

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 was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

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

BS2

High Hemizygotes in GnomAd4 at 6 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001303512.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PDZD4	NM_001303512.2	MANE Select	c.1808G>A	p.Gly603Asp	missense	Exon 8 of 8	NP_001290441.1	Q17RL8
PDZD4	NM_032512.5		c.1790G>A	p.Gly597Asp	missense	Exon 8 of 8	NP_115901.2
PDZD4	NM_001303515.2		c.1565G>A	p.Gly522Asp	missense	Exon 8 of 8	NP_001290444.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PDZD4	ENST00000393758.7	TSL:1 MANE Select	c.1808G>A	p.Gly603Asp	missense	Exon 8 of 8	ENSP00000377355.3	Q17RL8
PDZD4	ENST00000164640.8	TSL:1	c.1790G>A	p.Gly597Asp	missense	Exon 8 of 8	ENSP00000164640.4	Q76G19-1
PDZD4	ENST00000544474.5	TSL:1	c.1463G>A	p.Gly488Asp	missense	Exon 6 of 6	ENSP00000442033.1	Q76G19-2

Frequencies

GnomAD3 genomes

AF:

0.000176

AC:

AN:

113776

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.0000439

AC:

AN:

136663

AF XY:

0.0000718

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 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

African (AFR)

AF:

0.000426

AC:

AN:

25842

American (AMR)

AF:

0.00

AC:

AN:

33053

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18427

East Asian (EAS)

AF:

0.00

AC:

AN:

29635

South Asian (SAS)

AF:

0.00

AC:

AN:

51252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32809

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3881

European-Non Finnish (NFE)

AF:

0.00000120

AC:

AN:

832330

Other (OTH)

AF:

0.00

AC:

AN:

45020

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000176

AC:

AN:

113776

Hom.:

Cov.:

AF XY:

0.000167

AC XY:

AN XY:

35924

show subpopulations

African (AFR)

AF:

0.000605

AC:

AN:

31413

American (AMR)

AF:

0.00

AC:

AN:

10944

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2661

East Asian (EAS)

AF:

0.00

AC:

AN:

3601

South Asian (SAS)

AF:

0.00

AC:

AN:

2882

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6427

Middle Eastern (MID)

AF:

0.00

AC:

AN:

236

European-Non Finnish (NFE)

AF:

0.0000187

AC:

AN:

53385

Other (OTH)

AF:

0.00

AC:

AN:

1540

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000285

Hom.:

Bravo

AF:

0.000155

ExAC

AF:

0.00000865

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.18

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.77

M_CAP

Benign

0.074

MetaRNN

Benign

0.068

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

PhyloP100

2.0

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-1.3

REVEL

Benign

0.11

Sift

Benign

0.059

Sift4G

Benign

0.18

Polyphen

0.0

Vest4

0.20

MVP

0.62

MPC

1.1

ClinPred

0.033

GERP RS

3.9

Varity_R

0.17

gMVP

0.47

Mutation Taster

=99/1

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over