X-153804030-G-A

Position:

• chrX-153804030-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001303512.2(PDZD4):​c.1651C>T​(p.Arg551Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,043,426 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. 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)
  • Exomes 𝑓: 0.0000048 (0 hom. 3 hem.)
• Consequence: PDZD4 NM_001303512.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.751

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2223131).
• BS2: High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDZD4	NM_001303512.2	c.1651C>T	p.Arg551Cys	missense_variant	8/8	ENST00000393758.7	NP_001290441.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDZD4	ENST00000393758.7	c.1651C>T	p.Arg551Cys	missense_variant	8/8	1	NM_001303512.2	ENSP00000377355.3
PDZD4	ENST00000164640.8	c.1633C>T	p.Arg545Cys	missense_variant	8/8	1		ENSP00000164640.4
PDZD4	ENST00000544474.5	c.1306C>T	p.Arg436Cys	missense_variant	6/6	1		ENSP00000442033.1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome AF: 0.00000479 AC: 5 AN: 1043426 Hom.: 0 Cov.: 33 AF XY: 0.00000885 AC XY: 3 AN XY: 338966

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: 0.00000612

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 25

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 07, 2021

The c.1633C>T (p.R545C) alteration is located in exon 8 (coding exon 8) of the PDZD4 gene. This alteration results from a C to T substitution at nucleotide position 1633, causing the arginine (R) at amino acid position 545 to be replaced by a cysteine (C). 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	0.13
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.47	T;.;T
FATHMM_MKL	Benign	0.71	D
LIST_S2	Uncertain	0.92	D;D;D
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.22	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-2.9	D;D;.
REVEL	Benign	0.17
Sift	Uncertain	0.022	D;D;.
Sift4G	Benign	0.067	T;T;T
Polyphen		1.0	D;.;D
Vest4		0.17
MutPred		0.27		Loss of MoRF binding (P = 0.0139);.;.;
MVP		0.35
MPC		2.2
ClinPred		0.94	D
GERP RS		4.6
Varity_R		0.20
gMVP		0.55

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-153069485;