X-153807302-G-T

Variant names:

• chrX-153807302-G-T
• NM_001303512.2:c.382C>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001303512.2(PDZD4):​c.382C>A​(p.Arg128Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000912 in 1,096,220 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: PDZD4 NM_001303512.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.07

Genes affected

PDZD4 (HGNC:21167): (PDZ domain containing 4) Predicted to be located in cell cortex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36363477).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDZD4	NM_001303512.2	c.382C>A	p.Arg128Ser	missense_variant	Exon 3 of 8	ENST00000393758.7	NP_001290441.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDZD4	ENST00000393758.7	c.382C>A	p.Arg128Ser	missense_variant	Exon 3 of 8	1	NM_001303512.2	ENSP00000377355.3

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome AF: 9.12e-7 AC: 1 AN: 1096220 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 362296

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: 0.00

GnomAD4 genome Cov.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.54	D;T
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.87	D;D
M_CAP	Uncertain	0.27	D
MetaRNN	Benign	0.36	T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.2	M;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-3.6	D;.
REVEL	Benign	0.12
Sift	Benign	0.068	T;.
Sift4G	Benign	0.074	T;T
Polyphen		1.0	D;D
Vest4		0.47
MutPred		0.38		Gain of phosphorylation at R122 (P = 0.0185);.;
MVP		0.48
MPC		0.31
ClinPred		0.99	D
GERP RS		4.8
Varity_R		0.56
gMVP		0.78

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.

Other links and lift over

hg19: chrX-153072757;