Variant chrX-153804327-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001303512.2(PDZD4):c.1354A>G(p.Ser452Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000366 in 1,093,085 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 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: not found (cov: 25)

Exomes 𝑓: 0.0000037 ( 0 hom. 1 hem. )

Consequence

PDZD4
NM_001303512.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.704

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03338638).

BP6

Variant X-153804327-T-C is Benign according to our data. Variant chrX-153804327-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2534428.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDZD4	NM_001303512.2 linkuse as main transcript	c.1354A>G	p.Ser452Gly	missense_variant	8/8	ENST00000393758.7	NP_001290441.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDZD4	ENST00000393758.7 linkuse as main transcript	c.1354A>G	p.Ser452Gly	missense_variant	8/8	1	NM_001303512.2	ENSP00000377355	P4
PDZD4	ENST00000164640.8 linkuse as main transcript	c.1336A>G	p.Ser446Gly	missense_variant	8/8	1		ENSP00000164640	A1	Q76G19-1
PDZD4	ENST00000544474.5 linkuse as main transcript	c.1009A>G	p.Ser337Gly	missense_variant	6/6	1		ENSP00000442033		Q76G19-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000366

AC:

AN:

1093085

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

360395

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

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:

0.00000357

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Apr 07, 2023

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

0.051

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-1.1

CADD

Benign

1.1

DANN

Benign

0.87

DEOGEN2

Benign

0.14

T;.;T

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.66

T;T;T

M_CAP

Benign

0.0056

MetaRNN

Benign

0.033

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-1.1

N;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.97

N;N;.

REVEL

Benign

0.053

Sift

Benign

0.16

T;T;.

Sift4G

Benign

0.32

T;T;T

Polyphen

0.0

B;.;B

Vest4

0.021

MutPred

0.16

Loss of phosphorylation at S446 (P = 0.0189);.;.;

MVP

0.10

MPC

0.82

ClinPred

0.055

GERP RS

-7.5

Varity_R

0.076

gMVP

0.26

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over