Variant X-153804332-G-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.1349C>G(p.Ala450Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000883 in 113,235 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples 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: 25)

Consequence

PDZD4
NM_001303512.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0340

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=0.04036364).

BP6

Variant X-153804332-G-C is Benign according to our data. Variant chrX-153804332-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2567493.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 link	c.1349C>G	p.Ala450Gly	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.1349C>G	p.Ala450Gly	missense_variant	8/8	1	NM_001303512.2	ENSP00000377355.3	Q17RL8
PDZD4	ENST00000164640.8 link	c.1331C>G	p.Ala444Gly	missense_variant	8/8	1		ENSP00000164640.4	Q76G19-1
PDZD4	ENST00000544474.5 link	c.1004C>G	p.Ala335Gly	missense_variant	6/6	1		ENSP00000442033.1	Q76G19-2

Frequencies

GnomAD3 genomes

AF:

0.00000883

AC:

AN:

113235

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35365

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

Cov.:

GnomAD4 genome

AF:

0.00000883

AC:

AN:

113235

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35365

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

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

0.062

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-1.0

CADD

Benign

6.5

DANN

Benign

0.89

DEOGEN2

Benign

0.060

T;.;T

FATHMM_MKL

Benign

0.0094

LIST_S2

Benign

0.73

T;T;T

M_CAP

Benign

0.021

MetaRNN

Benign

0.040

T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

-1.4

N;.;.

PrimateAI

Benign

0.46

PROVEAN

Benign

1.6

N;N;N

REVEL

Benign

0.068

Sift

Benign

0.40

T;T;T

Sift4G

Benign

0.70

T;T;T

Polyphen

0.0

B;.;B

Vest4

0.038

MutPred

0.094

Loss of loop (P = 0.0512);.;.;

MVP

0.12

MPC

0.90

ClinPred

0.035

GERP RS

0.94

Varity_R

0.048

gMVP

0.40

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