Genetic Variant PDZD4:p.Gly504Ser (chrX-153804171-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.1510G>A(p.Gly504Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000111 in 1,176,469 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 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 0.000027 ( 0 hom., 1 hem., cov: 25)

Exomes 𝑓: 0.0000094 ( 0 hom. 4 hem. )

Consequence

PDZD4
NM_001303512.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.112

Publications

1 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=0.026434213).

BS2

High Hemizygotes in GnomAdExome4 at 4 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.1510G>A	p.Gly504Ser	missense	Exon 8 of 8	NP_001290441.1	Q17RL8
PDZD4	NM_032512.5		c.1492G>A	p.Gly498Ser	missense	Exon 8 of 8	NP_115901.2
PDZD4	NM_001303515.2		c.1267G>A	p.Gly423Ser	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.1510G>A	p.Gly504Ser	missense	Exon 8 of 8	ENSP00000377355.3	Q17RL8
PDZD4	ENST00000164640.8	TSL:1	c.1492G>A	p.Gly498Ser	missense	Exon 8 of 8	ENSP00000164640.4	Q76G19-1
PDZD4	ENST00000544474.5	TSL:1	c.1165G>A	p.Gly389Ser	missense	Exon 6 of 6	ENSP00000442033.1	Q76G19-2

Frequencies

GnomAD3 genomes

AF:

0.0000265

AC:

AN:

113022

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000713

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000161

AC:

AN:

124386

AF XY:

0.0000294

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000940

AC:

AN:

1063396

Hom.:

Cov.:

AF XY:

0.0000117

AC XY:

AN XY:

342240

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25743

American (AMR)

AF:

0.00

AC:

AN:

30748

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18558

East Asian (EAS)

AF:

0.00

AC:

AN:

28768

South Asian (SAS)

AF:

0.0000784

AC:

AN:

51005

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34150

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3591

European-Non Finnish (NFE)

AF:

0.00000726

AC:

AN:

826060

Other (OTH)

AF:

0.00

AC:

AN:

44773

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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:

0.0000265

AC:

AN:

113073

Hom.:

Cov.:

AF XY:

0.0000284

AC XY:

AN XY:

35237

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31255

American (AMR)

AF:

0.00

AC:

AN:

10858

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2654

East Asian (EAS)

AF:

0.00

AC:

AN:

3548

South Asian (SAS)

AF:

0.000716

AC:

AN:

2795

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6295

Middle Eastern (MID)

AF:

0.00

AC:

AN:

215

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

53231

Other (OTH)

AF:

0.00

AC:

AN:

1546

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.600

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:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000428

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

0.084

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.79

CADD

Benign

6.6

(source)

DANN

Benign

0.45

DEOGEN2

Benign

0.063

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.75

M_CAP

Benign

0.015

MetaRNN

Benign

0.026

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

PhyloP100

0.11

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.040

REVEL

Benign

0.12

Sift

Benign

0.40

Sift4G

Benign

0.72

Polyphen

0.77

Vest4

0.041

MutPred

0.17

Gain of helix (P = 0.0425)

MVP

0.43

MPC

0.89

ClinPred

0.045

GERP RS

4.1

Varity_R

0.087

gMVP

0.46

Mutation Taster

=98/2

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