Variant X-153804122-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_001303512.2(PDZD4):c.1559C>A(p.Pro520His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00002 in 1,150,583 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000088 ( 0 hom., 0 hem., cov: 26)

Exomes 𝑓: 0.000021 ( 0 hom. 8 hem. )

Consequence

PDZD4
NM_001303512.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.616

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=0.08765218).

BP6

Variant X-153804122-G-T is Benign according to our data. Variant chrX-153804122-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3305656.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDZD4	NM_001303512.2 link	c.1559C>A	p.Pro520His	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.1559C>A	p.Pro520His	missense_variant	8/8	1	NM_001303512.2	ENSP00000377355.3	Q17RL8
PDZD4	ENST00000164640.8 link	c.1541C>A	p.Pro514His	missense_variant	8/8	1		ENSP00000164640.4	Q76G19-1
PDZD4	ENST00000544474.5 link	c.1214C>A	p.Pro405His	missense_variant	6/6	1		ENSP00000442033.1	Q76G19-2

Frequencies

GnomAD3 genomes

AF:

0.00000882

AC:

AN:

113393

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35539

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000187

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000212

AC:

AN:

1037190

Hom.:

Cov.:

AF XY:

0.0000239

AC XY:

AN XY:

334308

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000258

Gnomad4 OTH exome

AF:

0.0000228

GnomAD4 genome

AF:

0.00000882

AC:

AN:

113393

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35539

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:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000187

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 07, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-1.1

CADD

Benign

2.5

DANN

Benign

0.64

DEOGEN2

Benign

0.11

T;.;T

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.51

T;T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.088

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.34

N;.;.

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.38

N;N;.

REVEL

Benign

0.014

Sift

Benign

0.19

T;T;.

Sift4G

Uncertain

0.056

T;D;T

Polyphen

0.0

B;.;B

Vest4

0.066

MutPred

0.15

Loss of glycosylation at P514 (P = 0.0308);.;.;

MVP

0.068

MPC

1.0

ClinPred

0.11

GERP RS

-1.2

Varity_R

0.083

gMVP

0.28

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