X-153805179-C-A

Variant names:

• chrX-153805179-C-A
• rs782194751
• NM_001303512.2:c.698G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001303512.2(PDZD4):​c.698G>T​(p.Arg233Leu) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R233Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 24)
• Consequence: PDZD4 NM_001303512.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.69
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30785817).

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.698G>T	p.Arg233Leu	missense	Exon 7 of 8	NP_001290441.1	Q17RL8
	PDZD4	NM_032512.5		c.680G>T	p.Arg227Leu	missense	Exon 7 of 8	NP_115901.2
	PDZD4	NM_001303515.2		c.455G>T	p.Arg152Leu	missense	Exon 7 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.698G>T	p.Arg233Leu	missense	Exon 7 of 8	ENSP00000377355.3	Q17RL8
	PDZD4	ENST00000164640.8	TSL:1	c.680G>T	p.Arg227Leu	missense	Exon 7 of 8	ENSP00000164640.4	Q76G19-1
	PDZD4	ENST00000544474.5	TSL:1	c.353G>T	p.Arg118Leu	missense	Exon 5 of 6	ENSP00000442033.1	Q76G19-2

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.53	D
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.96	D
M_CAP	Pathogenic	0.30	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M
PhyloP100		4.7
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.092
Sift	Benign	0.11	T
Sift4G	Benign	0.20	T
Polyphen		0.012	B
Vest4		0.45
MutPred		0.22		Loss of methylation at K223 (P = 0.0848)
MVP		0.36
MPC		1.1
ClinPred		0.83	D
GERP RS		5.2
Varity_R		0.30
gMVP		0.89
Mutation Taster		=84/16	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

dbSNP: rs782194751; hg19: chrX-153070634;