X-153804357-C-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001303512.2(PDZD4):ā€‹c.1324G>Cā€‹(p.Glu442Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000414 in 1,207,152 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 14 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.00022 ( 0 hom., 9 hem., cov: 25)
Exomes š‘“: 0.000023 ( 0 hom. 5 hem. )

Consequence

PDZD4
NM_001303512.2 missense

Scores

5
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.21
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.08165696).
BS2
High Hemizygotes in GnomAd4 at 9 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PDZD4NM_001303512.2 linkuse as main transcriptc.1324G>C p.Glu442Gln missense_variant 8/8 ENST00000393758.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PDZD4ENST00000393758.7 linkuse as main transcriptc.1324G>C p.Glu442Gln missense_variant 8/81 NM_001303512.2 P4
PDZD4ENST00000164640.8 linkuse as main transcriptc.1306G>C p.Glu436Gln missense_variant 8/81 A1Q76G19-1
PDZD4ENST00000544474.5 linkuse as main transcriptc.979G>C p.Glu327Gln missense_variant 6/61 Q76G19-2

Frequencies

GnomAD3 genomes
AF:
0.000221
AC:
25
AN:
113301
Hom.:
0
Cov.:
25
AF XY:
0.000254
AC XY:
9
AN XY:
35437
show subpopulations
Gnomad AFR
AF:
0.000769
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000923
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000448
AC:
8
AN:
178476
Hom.:
0
AF XY:
0.0000153
AC XY:
1
AN XY:
65326
show subpopulations
Gnomad AFR exome
AF:
0.000622
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000229
AC:
25
AN:
1093851
Hom.:
0
Cov.:
33
AF XY:
0.0000139
AC XY:
5
AN XY:
360981
show subpopulations
Gnomad4 AFR exome
AF:
0.000872
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:
0.00
Gnomad4 OTH exome
AF:
0.0000435
GnomAD4 genome
AF:
0.000221
AC:
25
AN:
113301
Hom.:
0
Cov.:
25
AF XY:
0.000254
AC XY:
9
AN XY:
35437
show subpopulations
Gnomad4 AFR
AF:
0.000769
Gnomad4 AMR
AF:
0.0000923
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.000140
ESP6500AA
AF:
0.000261
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000165
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 16, 2024The c.1306G>C (p.E436Q) alteration is located in exon 8 (coding exon 8) of the PDZD4 gene. This alteration results from a G to C substitution at nucleotide position 1306, causing the glutamic acid (E) at amino acid position 436 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.23
BayesDel_addAF
Benign
-0.61
T
BayesDel_noAF
Benign
-0.69
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.14
T;.;T
FATHMM_MKL
Uncertain
0.78
D
LIST_S2
Uncertain
0.92
D;D;D
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.082
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.2
M;.;.
MutationTaster
Benign
0.95
D;D;D
PrimateAI
Uncertain
0.56
T
PROVEAN
Benign
-0.82
N;N;.
REVEL
Benign
0.16
Sift
Benign
0.072
T;T;.
Sift4G
Benign
0.25
T;T;T
Polyphen
1.0
D;.;D
Vest4
0.14
MVP
0.33
MPC
1.7
ClinPred
0.088
T
GERP RS
4.9
Varity_R
0.48
gMVP
0.68

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.

Other links and lift over

dbSNP: rs372418261; hg19: chrX-153069812; API