chrX-153804082-G-A

Variant names:

• chrX-153804082-G-A
• rs945217605
• NM_001303512.2:c.1599C>T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_001303512.2(PDZD4):​c.1599C>T​(p.Phe533Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000048 in 1,042,487 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 0.0000048 (0 hom. 2 hem.)
• Consequence: PDZD4 NM_001303512.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.47

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 Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP7: Synonymous conserved (PhyloP=2.47 with no splicing effect.
• BS2: High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDZD4	NM_001303512.2	c.1599C>T	p.Phe533Phe	synonymous_variant	Exon 8 of 8	ENST00000393758.7	NP_001290441.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDZD4	ENST00000393758.7	c.1599C>T	p.Phe533Phe	synonymous_variant	Exon 8 of 8	1	NM_001303512.2	ENSP00000377355.3
PDZD4	ENST00000164640.8	c.1581C>T	p.Phe527Phe	synonymous_variant	Exon 8 of 8	1		ENSP00000164640.4
PDZD4	ENST00000544474.5	c.1254C>T	p.Phe418Phe	synonymous_variant	Exon 6 of 6	1		ENSP00000442033.1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome AF: 0.00000480 AC: 5 AN: 1042487 Hom.: 0 Cov.: 33 AF XY: 0.00000590 AC XY: 2 AN XY: 339025

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000611

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 25

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	10
DANN	Benign	0.65

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

LitVar

Other links and lift over

dbSNP: rs945217605; hg19: chrX-153069537;