X-153804021-G-C

Position:

• chrX-153804021-G-C

Variant summary

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

The NM_001303512.2(PDZD4):​c.1660C>G​(p.Arg554Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: 1.20

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=0.10565862).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDZD4	NM_001303512.2	c.1660C>G	p.Arg554Gly	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.1660C>G	p.Arg554Gly	missense_variant	8/8	1	NM_001303512.2	ENSP00000377355	P4
PDZD4	ENST00000164640.8	c.1642C>G	p.Arg548Gly	missense_variant	8/8	1		ENSP00000164640	A1
PDZD4	ENST00000544474.5	c.1315C>G	p.Arg439Gly	missense_variant	6/6	1		ENSP00000442033

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome Cov.: 33

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

May 16, 2023

The c.1642C>G (p.R548G) 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 1642, causing the arginine (R) at amino acid position 548 to be replaced by a glycine (G). 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	0.098
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	15
DANN	Benign	0.92
DEOGEN2	Benign	0.24	T;.;T
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.78	T;T;T
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.96	L;.;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.2	N;N;D
REVEL	Benign	0.040
Sift	Benign	0.12	T;T;D
Sift4G	Benign	0.36	T;T;T
Polyphen		0.19	B;.;B
Vest4		0.094
MutPred		0.28		Loss of solvent accessibility (P = 0.0044);.;.;
MVP		0.13
MPC		1.2
ClinPred		0.046	T
GERP RS		3.7
Varity_R		0.22
gMVP		0.72

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-153069476;