chrX:153803771:1:A

You've typed SPDI variant. Standard notation is: chrX-153803772-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 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

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 4 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDZD4	NM_001303512.2	c.1909G>T	p.Asp637Tyr	missense_variant	8/8	ENST00000393758.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDZD4	ENST00000393758.7	c.1909G>T	p.Asp637Tyr	missense_variant	8/8	1	NM_001303512.2	P4
PDZD4	ENST00000164640.8	c.1891G>T	p.Asp631Tyr	missense_variant	8/8	1		A1
PDZD4	ENST00000544474.5	c.1564G>T	p.Asp522Tyr	missense_variant	6/6	1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;.;T

FATHMM_MKL

Pathogenic

1.0

D

LIST_S2

Pathogenic

1.0

D;D;D

M_CAP

Pathogenic

0.60

D

MetaRNN

Pathogenic

0.87

D;D;D

MetaSVM

Uncertain

-0.15

T

MutationAssessor

Uncertain

2.7

M;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.86

D

PROVEAN

Pathogenic

-8.7

D;D;.

REVEL

Pathogenic

0.67

Sift

Pathogenic

0.0

D;D;.

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;.;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

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-153069227;