X-153804758-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001303512.2(PDZD4):​c.923C>T​(p.Pro308Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000182 in 1,097,272 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 Uncertain significance (no stars).

Frequency

Genomes: not found (cov: 24)
Exomes 𝑓: 0.0000018 ( 0 hom. 0 hem. )

Consequence

PDZD4
NM_001303512.2 missense

Scores

2
15

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 1.50
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 Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.080632).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PDZD4NM_001303512.2 linkuse as main transcriptc.923C>T p.Pro308Leu missense_variant 8/8 ENST00000393758.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PDZD4ENST00000393758.7 linkuse as main transcriptc.923C>T p.Pro308Leu missense_variant 8/81 NM_001303512.2 P4
PDZD4ENST00000164640.8 linkuse as main transcriptc.905C>T p.Pro302Leu missense_variant 8/81 A1Q76G19-1
PDZD4ENST00000544474.5 linkuse as main transcriptc.578C>T p.Pro193Leu missense_variant 6/61 Q76G19-2

Frequencies

GnomAD3 genomes
Cov.:
24
GnomAD3 exomes
AF:
0.00000550
AC:
1
AN:
181911
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
67465
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:
0.0000124
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000182
AC:
2
AN:
1097272
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
363244
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000119
Gnomad4 OTH exome
AF:
0.0000217
GnomAD4 genome
Cov.:
24
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Autism Uncertain:1
Uncertain significance, no assertion criteria providedresearchCentre for Addiction & Mental Health, Centre for Addiction & Mental Health-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.062
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.75
CADD
Benign
18
DANN
Benign
0.97
DEOGEN2
Benign
0.17
T;.;T
FATHMM_MKL
Uncertain
0.83
D
LIST_S2
Benign
0.85
D;D;D
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.081
T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
1.4
L;.;.
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.46
T
PROVEAN
Benign
-1.2
N;N;.
REVEL
Benign
0.029
Sift
Uncertain
0.024
D;D;.
Sift4G
Benign
0.30
T;T;T
Polyphen
0.025
B;.;B
Vest4
0.087
MutPred
0.21
Loss of glycosylation at P302 (P = 0.0569);.;.;
MVP
0.10
MPC
1.0
ClinPred
0.14
T
GERP RS
4.3
Varity_R
0.081
gMVP
0.85

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: rs782527593; hg19: chrX-153070213; API