rs782552006

Variant names:

• chrX-153803925-G-A
• rs782552006
• NM_001303512.2:c.1756C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-153803925-G-A
• chrX-153803925-G-C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001303512.2(PDZD4):​c.1756C>T​(p.His586Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000566 in 1,060,283 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 26)
  • Exomes 𝑓: 0.0000057 (0 hom. 3 hem.)
• Consequence: PDZD4 NM_001303512.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.83
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.14056906).
• BS2: High Hemizygotes in GnomAdExome4 at 3 gene

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.1756C>T	p.His586Tyr	missense	Exon 8 of 8	NP_001290441.1	Q17RL8
	PDZD4	NM_032512.5		c.1738C>T	p.His580Tyr	missense	Exon 8 of 8	NP_115901.2
	PDZD4	NM_001303515.2		c.1513C>T	p.His505Tyr	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.1756C>T	p.His586Tyr	missense	Exon 8 of 8	ENSP00000377355.3	Q17RL8
	PDZD4	ENST00000164640.8	TSL:1	c.1738C>T	p.His580Tyr	missense	Exon 8 of 8	ENSP00000164640.4	Q76G19-1
	PDZD4	ENST00000544474.5	TSL:1	c.1411C>T	p.His471Tyr	missense	Exon 6 of 6	ENSP00000442033.1	Q76G19-2

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD2 exomes AF: 0.0000456 AC: 5 AN: 109545 AF XY: 0.0000928

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000240

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000566 AC: 6 AN: 1060283 Hom.: 0 Cov.: 33 AF XY: 0.00000875 AC XY: 3 AN XY: 342663

African (AFR) AF: 0.00 AC: 0 AN: 25349

American (AMR) AF: 0.000199 AC: 6 AN: 30169

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18574

East Asian (EAS) AF: 0.00 AC: 0 AN: 27937

South Asian (SAS) AF: 0.00 AC: 0 AN: 50499

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33974

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3737

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 825395

Other (OTH) AF: 0.00 AC: 0 AN: 44649

GnomAD4 genome Cov.: 26

ExAC AF: 0.0000287 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.67	D
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		7.8
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.17
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.071	T
Polyphen		0.066	B
Vest4		0.20
MutPred		0.28		Gain of phosphorylation at H580 (P = 0.0068)
MVP		0.28
MPC		1.2
ClinPred		0.38	T
GERP RS		5.7
Varity_R		0.62
gMVP		0.64
Mutation Taster		=99/1	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: rs782552006; hg19: chrX-153069380;