X-153804122-G-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001303512.2(PDZD4):ā€‹c.1559C>Gā€‹(p.Pro520Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000209 in 1,150,636 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 69 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P520H) has been classified as Likely benign.

Frequency

Genomes: š‘“ 0.00060 ( 0 hom., 18 hem., cov: 26)
Exomes š‘“: 0.00017 ( 0 hom. 51 hem. )

Consequence

PDZD4
NM_001303512.2 missense

Scores

16

Clinical Significance

Uncertain significance criteria provided, single submitter U: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]

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=0.0052959323).
BS2
High Hemizygotes in GnomAd4 at 18 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PDZD4NM_001303512.2 linkuse as main transcriptc.1559C>G p.Pro520Arg missense_variant 8/8 ENST00000393758.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PDZD4ENST00000393758.7 linkuse as main transcriptc.1559C>G p.Pro520Arg missense_variant 8/81 NM_001303512.2 P4
PDZD4ENST00000164640.8 linkuse as main transcriptc.1541C>G p.Pro514Arg missense_variant 8/81 A1Q76G19-1
PDZD4ENST00000544474.5 linkuse as main transcriptc.1214C>G p.Pro405Arg missense_variant 6/61 Q76G19-2

Frequencies

GnomAD3 genomes
AF:
0.000600
AC:
68
AN:
113392
Hom.:
0
Cov.:
26
AF XY:
0.000507
AC XY:
18
AN XY:
35538
show subpopulations
Gnomad AFR
AF:
0.00176
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000184
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00422
Gnomad NFE
AF:
0.000187
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000351
AC:
31
AN:
88205
Hom.:
0
AF XY:
0.000229
AC XY:
6
AN XY:
26181
show subpopulations
Gnomad AFR exome
AF:
0.00193
Gnomad AMR exome
AF:
0.000672
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:
0.000243
Gnomad OTH exome
AF:
0.000362
GnomAD4 exome
AF:
0.000166
AC:
172
AN:
1037191
Hom.:
0
Cov.:
33
AF XY:
0.000153
AC XY:
51
AN XY:
334309
show subpopulations
Gnomad4 AFR exome
AF:
0.00165
Gnomad4 AMR exome
AF:
0.000925
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:
0.000102
Gnomad4 OTH exome
AF:
0.000410
GnomAD4 genome
AF:
0.000599
AC:
68
AN:
113445
Hom.:
0
Cov.:
26
AF XY:
0.000506
AC XY:
18
AN XY:
35601
show subpopulations
Gnomad4 AFR
AF:
0.00175
Gnomad4 AMR
AF:
0.000183
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000188
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000304
Hom.:
2
Bravo
AF:
0.000812
ExAC
AF:
0.000143
AC:
13

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 GeneticsNov 14, 2023The c.1541C>G (p.P514R) alteration is located in exon 8 (coding exon 8) of the PDZD4 gene. This alteration results from a C to G substitution at nucleotide position 1541, causing the proline (P) at amino acid position 514 to be replaced by an arginine (R). 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
0.088
BayesDel_addAF
Benign
-0.82
T
BayesDel_noAF
Benign
-0.97
CADD
Benign
1.3
DANN
Benign
0.59
DEOGEN2
Benign
0.088
T;.;T
FATHMM_MKL
Benign
0.080
N
LIST_S2
Benign
0.57
T;T;T
MetaRNN
Benign
0.0053
T;T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
0.34
N;.;.
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.44
T
PROVEAN
Benign
-0.32
N;N;.
REVEL
Benign
0.023
Sift
Benign
0.54
T;T;.
Sift4G
Benign
0.28
T;T;T
Polyphen
0.0080
B;.;B
Vest4
0.078
MVP
0.093
MPC
0.94
ClinPred
0.0016
T
GERP RS
-1.2
Varity_R
0.045
gMVP
0.37

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: rs544558369; hg19: chrX-153069577; API