X-153804810-C-T

Variant names:

• chrX-153804810-C-T
• NM_001303512.2:c.871G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001303512.2(PDZD4):​c.871G>A​(p.Glu291Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 25)
• Consequence: PDZD4 NM_001303512.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.05

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2166326).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDZD4	NM_001303512.2	c.871G>A	p.Glu291Lys	missense_variant	Exon 8 of 8	ENST00000393758.7	NP_001290441.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDZD4	ENST00000393758.7	c.871G>A	p.Glu291Lys	missense_variant	Exon 8 of 8	1	NM_001303512.2	ENSP00000377355.3
PDZD4	ENST00000164640.8	c.853G>A	p.Glu285Lys	missense_variant	Exon 8 of 8	1		ENSP00000164640.4
PDZD4	ENST00000544474.5	c.526G>A	p.Glu176Lys	missense_variant	Exon 6 of 6	1		ENSP00000442033.1
PDZD4	ENST00000484792.5	n.*69G>A		downstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 25

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 28, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.853G>A (p.E285K) alteration is located in exon 8 (coding exon 8) of the PDZD4 gene. This alteration results from a G to A substitution at nucleotide position 853, causing the glutamic acid (E) at amino acid position 285 to be replaced by a lysine (K). 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	Pathogenic	0.72
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.67	D;.;T
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D;D;D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.22	T;T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.8	M;.;.
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-3.1	D;D;.
REVEL	Benign	0.13
Sift	Uncertain	0.0030	D;D;.
Sift4G	Uncertain	0.016	D;D;D
Polyphen		0.98	D;.;D
Vest4		0.15
MutPred		0.26		Gain of ubiquitination at E285 (P = 9e-04);.;.;
MVP		0.29
MPC		1.7
ClinPred		0.96	D
GERP RS		5.2
Varity_R		0.41
gMVP		0.94

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-153070265; COSMIC: COSV105035312; COSMIC: COSV105035312;