chrX-153803772-C-A

Variant names:

• chrX-153803772-C-A
• NM_001303512.2:c.1909G>T
• PDZD4 p.Asp637Tyr

GermlineCancer (beta)

Variant summary

Our verdict is Uncertain significance.

+3 Uncertain · Warm

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received 3 classification points (ACMG Germline Pathogenicity v2019). PM2PP3

The NM_001303512.2(PDZD4):c.1909G>T (p.Asp637Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. In-silico predictor (REVEL) classifies this variant as likely damaging/oncogenic. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. 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, Jul 2025]

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Uncertain_significance. The variant received 3 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	PM2Absent/extremely low in population databases		Absent from gnomAD (AR/unknown gene) — PM2; Absent from gnomAD at well-covered site (MOI: unknown) (threshold 0.001) — PM2 moderate.
	PP3Computational evidence supports damaging effect		Germline meta computational scorer (REVEL/MetaRNN/BayesDel) predicts damaging effect — supporting evidence (PP3); Splicing verdict: not pathogenic.; Germline computational verdict: pathogenic (Supporting).

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_001303512.2. You can select a different transcript below to see updated classification 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	Prot: NP_001290441.1 UniProt:
	PDZD4 NM_032512.5		c.1891G>T p.Asp631Tyr	missense	Exon 8 of 8	Prot: NP_115901.2
	PDZD4 NM_001303515.2		c.1666G>T p.Asp556Tyr	missense	Exon 8 of 8	Prot: NP_001290444.1

PDZD4 NM_001303512.2

MANE Select

HGVSc / HGVSpc.1909G>Tp.Asp637Tyr

Exon rankExon 8 of 8

missense

Prot: NP_001290441.1UniProt: F6S393Q17RL8

PDZD4 NM_032512.5

HGVSc / HGVSpc.1891G>Tp.Asp631Tyr

Exon rankExon 8 of 8

missense

Prot: NP_115901.2

PDZD4 NM_001303515.2

HGVSc / HGVSpc.1666G>Tp.Asp556Tyr

Exon rankExon 8 of 8

missense

Prot: NP_001290444.1

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	PDZD4 ENST00000393758.7	TSL:1MANE Select	c.1909G>T p.Asp637Tyr	missense	Exon 8 of 8	Prot: ENSP00000377355.3 UniProt:
	PDZD4 ENST00000164640.8	TSL:1	c.1891G>T p.Asp631Tyr	missense	Exon 8 of 8	Prot: ENSP00000164640.4 UniProt:
	PDZD4 ENST00000544474.5	TSL:1	c.1564G>T p.Asp522Tyr	missense	Exon 6 of 6	Prot: ENSP00000442033.1 UniProt:

PDZD4 ENST00000393758.7

TSL:1MANE Select

HGVSc / HGVSpc.1909G>Tp.Asp637Tyr

Exon rankExon 8 of 8

missense

Prot: ENSP00000377355.3UniProt: F6S393

PDZD4 ENST00000164640.8

TSL:1

HGVSc / HGVSpc.1891G>Tp.Asp631Tyr

Exon rankExon 8 of 8

missense

Prot: ENSP00000164640.4UniProt: Q76G19-1

PDZD4 ENST00000544474.5

TSL:1

HGVSc / HGVSpc.1564G>Tp.Asp522Tyr

Exon rankExon 6 of 6

missense

Prot: ENSP00000442033.1UniProt: Q76G19-2

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 3 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:25
GnomAD4 exome	AF:	AC:	Hom:	AN:	Cov:33
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:25

Showing 3 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Pathogenic	27
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
FuncVEP CTI	Pathogenic	0.99
GPN-Star LLR	N/A	-9.8
GPN-Star score	N/A	9.8
LIST_S2	Pathogenic	1.0	D
M_CAP	Pathogenic	0.60	D
MetaRNN	Pathogenic	0.87	D
MetaSVM	Uncertain	-0.15	T
Mutation Taster	N/A	31/69	disease causing
MutationAssessor	Uncertain	2.7	M
PhyloP100	Uncertain	6.1
popEVE	Benign	-4.6
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-8.7	D
REVEL	Pathogenic	0.67
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Varity_R	N/A	0.97
VESM-3B	Benign	-15

Showing 26 of 26 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0
SpliceAI score (max)	Benign	0.0	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

hg19: chrX-153069227;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar