Variant chrX-153804253-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001303512.2(PDZD4):c.1428C>T(p.Ala476Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000796 in 1,207,738 control chromosomes in the GnomAD database, including 2 homozygotes. There are 298 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00057 ( 1 hom., 18 hem., cov: 25)

Exomes 𝑓: 0.00082 ( 1 hom. 280 hem. )

Consequence

PDZD4
NM_001303512.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.83

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant X-153804253-G-A is Benign according to our data. Variant chrX-153804253-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2661736.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 18 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDZD4	NM_001303512.2 linkuse as main transcript	c.1428C>T	p.Ala476Ala	synonymous_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.1428C>T	p.Ala476Ala	synonymous_variant	8/8	1	NM_001303512.2	ENSP00000377355.3	Q17RL8
PDZD4	ENST00000164640.8 linkuse as main transcript	c.1410C>T	p.Ala470Ala	synonymous_variant	8/8	1		ENSP00000164640.4	Q76G19-1
PDZD4	ENST00000544474.5 linkuse as main transcript	c.1083C>T	p.Ala361Ala	synonymous_variant	6/6	1		ENSP00000442033.1	Q76G19-2

Frequencies

GnomAD3 genomes

AF:

0.000574

AC:

AN:

113253

Hom.:

Cov.:

AF XY:

0.000509

AC XY:

AN XY:

35389

show subpopulations

Gnomad AFR

AF:

0.0000320

Gnomad AMI

AF:

0.0206

Gnomad AMR

AF:

0.000184

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00111

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000750

Gnomad OTH

AF:

0.000648

GnomAD3 exomes

AF:

0.000546

AC:

AN:

175847

Hom.:

AF XY:

0.000439

AC XY:

AN XY:

63841

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000184

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000960

Gnomad NFE exome

AF:

0.000947

Gnomad OTH exome

AF:

0.000693

GnomAD4 exome

AF:

0.000819

AC:

896

AN:

1094431

Hom.:

Cov.:

AF XY:

0.000775

AC XY:

280

AN XY:

361119

show subpopulations

Gnomad4 AFR exome

AF:

0.0000759

Gnomad4 AMR exome

AF:

0.000171

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00124

Gnomad4 NFE exome

AF:

0.000963

Gnomad4 OTH exome

AF:

0.000654

GnomAD4 genome

AF:

0.000574

AC:

AN:

113307

Hom.:

Cov.:

AF XY:

0.000508

AC XY:

AN XY:

35453

show subpopulations

Gnomad4 AFR

AF:

0.0000319

Gnomad4 AMR

AF:

0.000184

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00111

Gnomad4 NFE

AF:

0.000751

Gnomad4 OTH

AF:

0.000640

Alfa

AF:

0.000261

Hom.:

Bravo

AF:

0.000706

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

PDZD4: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.82

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