Variant X-153803412-C-T 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.2269G>A(p.Ala757Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000306 in 1,143,690 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 1 hem., cov: 25)

Exomes 𝑓: 0.000031 ( 0 hom. 9 hem. )

Consequence

PDZD4
NM_001303512.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.26

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 (MetaRNN=0.02868563).

BP6

Variant X-153803412-C-T is Benign according to our data. Variant chrX-153803412-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2253817.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDZD4	NM_001303512.2 linkuse as main transcript	c.2269G>A	p.Ala757Thr	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 linkuse as main transcript	c.2269G>A	p.Ala757Thr	missense_variant	8/8	1	NM_001303512.2	ENSP00000377355.3	Q17RL8
PDZD4	ENST00000164640.8 linkuse as main transcript	c.2251G>A	p.Ala751Thr	missense_variant	8/8	1		ENSP00000164640.4	Q76G19-1
PDZD4	ENST00000544474.5 linkuse as main transcript	c.1924G>A	p.Ala642Thr	missense_variant	6/6	1		ENSP00000442033.1	Q76G19-2

Frequencies

GnomAD3 genomes

AF:

0.0000266

AC:

AN:

112774

Hom.:

Cov.:

AF XY:

0.0000286

AC XY:

AN XY:

34930

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:

0.0000565

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000789

AC:

AN:

126749

Hom.:

AF XY:

0.00

AC XY:

AN XY:

42467

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:

0.00

Gnomad NFE exome

AF:

0.0000165

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000310

AC:

AN:

1030916

Hom.:

Cov.:

AF XY:

0.0000271

AC XY:

AN XY:

332566

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:

0.0000224

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000357

Gnomad4 OTH exome

AF:

0.0000464

GnomAD4 genome

AF:

0.0000266

AC:

AN:

112774

Hom.:

Cov.:

AF XY:

0.0000286

AC XY:

AN XY:

34930

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:

0.0000565

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000378

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

Oct 06, 2021

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

0.056

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.62

DANN

Benign

0.81

DEOGEN2

Benign

0.087

T;.;T

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.75

T;T;T

M_CAP

Benign

0.039

MetaRNN

Benign

0.029

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.55

N;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

0.79

N;N;.

REVEL

Benign

0.088

Sift

Benign

1.0

T;T;.

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

B;.;B

Vest4

0.057

MutPred

0.21

Loss of catalytic residue at M746 (P = 0.0205);.;.;

MVP

0.25

MPC

0.87

ClinPred

0.023

GERP RS

3.5

Varity_R

0.022

gMVP

0.65

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