Variant chrX-153804171-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.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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 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

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=0.026434213).

BS2

High Hemizygotes in GnomAdExome4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDZD4	NM_001303512.2 link	c.1510G>A	p.Gly504Ser	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 link	c.1510G>A	p.Gly504Ser	missense_variant	8/8	1	NM_001303512.2	ENSP00000377355.3	Q17RL8
PDZD4	ENST00000164640.8 link	c.1492G>A	p.Gly498Ser	missense_variant	8/8	1		ENSP00000164640.4	Q76G19-1
PDZD4	ENST00000544474.5 link	c.1165G>A	p.Gly389Ser	missense_variant	6/6	1		ENSP00000442033.1	Q76G19-2

Frequencies

GnomAD3 genomes

AF:

0.0000265

AC:

AN:

113022

Hom.:

Cov.:

AF XY:

0.0000284

AC XY:

AN XY:

35176

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

GnomAD3 exomes

AF:

0.0000161

AC:

AN:

124386

Hom.:

AF XY:

0.0000294

AC XY:

AN XY:

33964

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 SAS exome

AF:

0.000143

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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000784

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000726

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000265

AC:

AN:

113073

Hom.:

Cov.:

AF XY:

0.0000284

AC XY:

AN XY:

35237

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000716

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.0000428

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

Sep 02, 2024

The c.1492G>A (p.G498S) 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 1492, causing the glycine (G) at amino acid position 498 to be replaced by a serine (S). 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

0.084

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.79

CADD

Benign

6.6

DANN

Benign

0.45

DEOGEN2

Benign

0.063

T;.;T

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.75

T;T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.026

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;.;.

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.040

N;N;.

REVEL

Benign

0.12

Sift

Benign

0.40

T;T;.

Sift4G

Benign

0.72

T;T;T

Polyphen

0.77

P;.;B

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

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