chrX:153803771:1:A

You've typed an SPDI variant (sequence:position:deletion:insertion), where the position is zero-based, unlike in chromosome-position-reference-alternate.

Variant names:

• chrX-153803772-C-A
• NM_001303512.2:c.1909G>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001303512.2(PDZD4):​c.1909G>T​(p.Asp637Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 25)
• Consequence: PDZD4 NM_001303512.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.10
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.871

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.1909G>T	p.Asp637Tyr	missense	Exon 8 of 8	NP_001290441.1
	PDZD4	NM_032512.5		c.1891G>T	p.Asp631Tyr	missense	Exon 8 of 8	NP_115901.2
	PDZD4	NM_001303515.2		c.1666G>T	p.Asp556Tyr	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.1909G>T	p.Asp637Tyr	missense	Exon 8 of 8	ENSP00000377355.3
	PDZD4	ENST00000164640.8	TSL:1	c.1891G>T	p.Asp631Tyr	missense	Exon 8 of 8	ENSP00000164640.4
	PDZD4	ENST00000544474.5	TSL:1	c.1564G>T	p.Asp522Tyr	missense	Exon 6 of 6	ENSP00000442033.1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.25
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.80	D
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Pathogenic	1.0	D
M_CAP	Pathogenic	0.60	D
MetaRNN	Pathogenic	0.87	D
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		6.1
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-8.7	D
REVEL	Pathogenic	0.67
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.85
MutPred		0.58		Gain of catalytic residue at D631 (P = 0.0045)
MVP		0.68
MPC		2.2
ClinPred		1.0	D
GERP RS		5.7
Varity_R		0.97
gMVP		1.0
Mutation Taster		=31/69	disease causing

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-153069227;