Variant X-153804167-T-C 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.1514A>G(p.Asn505Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00043 in 1,172,612 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 160 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 0.00014 ( 0 hom., 4 hem., cov: 25)

Exomes 𝑓: 0.00046 ( 0 hom. 156 hem. )

Consequence

PDZD4
NM_001303512.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.81

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=0.017238766).

BS2

High Hemizygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDZD4	NM_001303512.2 linkuse as main transcript	c.1514A>G	p.Asn505Ser	missense_variant	8/8	ENST00000393758.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDZD4	ENST00000393758.7 linkuse as main transcript	c.1514A>G	p.Asn505Ser	missense_variant	8/8	1	NM_001303512.2	P4
PDZD4	ENST00000164640.8 linkuse as main transcript	c.1496A>G	p.Asn499Ser	missense_variant	8/8	1		A1	Q76G19-1
PDZD4	ENST00000544474.5 linkuse as main transcript	c.1169A>G	p.Asn390Ser	missense_variant	6/6	1			Q76G19-2

Frequencies

GnomAD3 genomes

AF:

0.000142

AC:

AN:

112291

Hom.:

Cov.:

AF XY:

0.000116

AC XY:

AN XY:

34559

show subpopulations

Gnomad AFR

AF:

0.0000323

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:

0.000323

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000245

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000116

AC:

AN:

120375

Hom.:

AF XY:

0.0000917

AC XY:

AN XY:

32729

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:

0.00

Gnomad FIN exome

AF:

0.000339

Gnomad NFE exome

AF:

0.000224

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000460

AC:

488

AN:

1060270

Hom.:

Cov.:

AF XY:

0.000458

AC XY:

156

AN XY:

340770

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000329

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000178

Gnomad4 NFE exome

AF:

0.000573

Gnomad4 OTH exome

AF:

0.000202

GnomAD4 genome

AF:

0.000142

AC:

AN:

112342

Hom.:

Cov.:

AF XY:

0.000116

AC XY:

AN XY:

34620

show subpopulations

Gnomad4 AFR

AF:

0.0000322

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000323

Gnomad4 NFE

AF:

0.000245

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000285

Hom.:

Bravo

AF:

0.000136

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000459

AC:

ExAC

AF:

0.000120

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

Feb 28, 2023

The c.1496A>G (p.N499S) alteration is located in exon 8 (coding exon 8) of the PDZD4 gene. This alteration results from a A to G substitution at nucleotide position 1496, causing the asparagine (N) at amino acid position 499 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

0.085

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.91

CADD

Benign

DANN

Benign

0.32

DEOGEN2

Benign

0.068

T;.;T

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.72

T;T;T

M_CAP

Benign

0.030

MetaRNN

Benign

0.017

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.60

N;.;.

MutationTaster

Benign

0.87

D;D;D

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.040

N;N;.

REVEL

Benign

0.11

Sift

Benign

0.96

T;T;.

Sift4G

Benign

0.93

T;T;T

Polyphen

0.26

B;.;B

Vest4

0.14

MVP

0.40

MPC

0.74

ClinPred

0.057

GERP RS

5.3

Varity_R

0.056

gMVP

0.15

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