NM_001303512.2:c.1523T>G

Variant names:

• chrX-153804158-A-C
• NM_001303512.2:c.1523T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001303512.2(PDZD4):​c.1523T>G​(p.Leu508Trp) 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. 12/21 in silico tools predict 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: 1.98
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23063678).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001303512.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDZD4	NM_001303512.2	MANE Select	c.1523T>G	p.Leu508Trp	missense	Exon 8 of 8	NP_001290441.1	Q17RL8
	PDZD4	NM_032512.5		c.1505T>G	p.Leu502Trp	missense	Exon 8 of 8	NP_115901.2
	PDZD4	NM_001303515.2		c.1280T>G	p.Leu427Trp	missense	Exon 8 of 8	NP_001290444.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDZD4	ENST00000393758.7	TSL:1 MANE Select	c.1523T>G	p.Leu508Trp	missense	Exon 8 of 8	ENSP00000377355.3	Q17RL8
	PDZD4	ENST00000164640.8	TSL:1	c.1505T>G	p.Leu502Trp	missense	Exon 8 of 8	ENSP00000164640.4	Q76G19-1
	PDZD4	ENST00000544474.5	TSL:1	c.1178T>G	p.Leu393Trp	missense	Exon 6 of 6	ENSP00000442033.1	Q76G19-2

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 25

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Uncertain	24
DANN	Benign	0.96
DEOGEN2	Benign	0.26	T
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	2.0	M
PhyloP100		2.0
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.14
Sift	Benign	0.085	T
Sift4G	Benign	0.17	T
Polyphen		1.0	D
Vest4		0.35
MutPred		0.17		Gain of MoRF binding (P = 0.028)
MVP		0.50
MPC		2.5
ClinPred		0.62	D
GERP RS		5.3
Varity_R		0.16
gMVP		0.63
Mutation Taster		=59/41	polymorphism

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

Other links and lift over

hg19: chrX-153069613;