chrX-153804122-G-C

Variant names:

• chrX-153804122-G-C
• rs544558369
• NM_001303512.2:c.1559C>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001303512.2(PDZD4):​c.1559C>G​(p.Pro520Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000209 in 1,150,636 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 69 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P520H) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00060 (0 hom., 18 hem., cov: 26)
  • Exomes 𝑓: 0.00017 (0 hom. 51 hem.)
• Consequence: PDZD4 NM_001303512.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.616
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0052959323).
• BS2: High Hemizygotes in GnomAd4 at 18 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.1559C>G	p.Pro520Arg	missense	Exon 8 of 8	NP_001290441.1	Q17RL8
	PDZD4	NM_032512.5		c.1541C>G	p.Pro514Arg	missense	Exon 8 of 8	NP_115901.2
	PDZD4	NM_001303515.2		c.1316C>G	p.Pro439Arg	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.1559C>G	p.Pro520Arg	missense	Exon 8 of 8	ENSP00000377355.3	Q17RL8
	PDZD4	ENST00000164640.8	TSL:1	c.1541C>G	p.Pro514Arg	missense	Exon 8 of 8	ENSP00000164640.4	Q76G19-1
	PDZD4	ENST00000544474.5	TSL:1	c.1214C>G	p.Pro405Arg	missense	Exon 6 of 6	ENSP00000442033.1	Q76G19-2

Frequencies

GnomAD3 genomes AF: 0.000600 AC: 68 AN: 113392 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.00176

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000184

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00422

Gnomad NFE AF: 0.000187

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000351 AC: 31 AN: 88205 AF XY: 0.000229

Gnomad AFR exome AF: 0.00193

Gnomad AMR exome AF: 0.000672

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000243

Gnomad OTH exome AF: 0.000362

GnomAD4 exome AF: 0.000166 AC: 172 AN: 1037191 Hom.: 0 Cov.: 33 AF XY: 0.000153 AC XY: 51 AN XY: 334309

African (AFR) AF: 0.00165 AC: 41 AN: 24823

American (AMR) AF: 0.000925 AC: 25 AN: 27026

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18024

East Asian (EAS) AF: 0.00 AC: 0 AN: 27106

South Asian (SAS) AF: 0.00 AC: 0 AN: 48318

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29099

Middle Eastern (MID) AF: 0.00135 AC: 5 AN: 3708

European-Non Finnish (NFE) AF: 0.000102 AC: 83 AN: 815208

Other (OTH) AF: 0.000410 AC: 18 AN: 43879

GnomAD4 genome AF: 0.000599 AC: 68 AN: 113445 Hom.: 0 Cov.: 26 AF XY: 0.000506 AC XY: 18 AN XY: 35601

African (AFR) AF: 0.00175 AC: 55 AN: 31354

American (AMR) AF: 0.000183 AC: 2 AN: 10904

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2657

East Asian (EAS) AF: 0.00 AC: 0 AN: 3555

South Asian (SAS) AF: 0.00 AC: 0 AN: 2834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6361

Middle Eastern (MID) AF: 0.00463 AC: 1 AN: 216

European-Non Finnish (NFE) AF: 0.000188 AC: 10 AN: 53329

Other (OTH) AF: 0.00 AC: 0 AN: 1556

Alfa AF: 0.000304 Hom.: 2

Bravo AF: 0.000812

ExAC AF: 0.000143 AC: 13

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	0.088
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.3
DANN	Benign	0.59
DEOGEN2	Benign	0.088	T
FATHMM_MKL	Benign	0.080	N
LIST_S2	Benign	0.57	T
MetaRNN	Benign	0.0053	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.62
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.32	N
REVEL	Benign	0.023
Sift	Benign	0.54	T
Sift4G	Benign	0.28	T
Polyphen		0.0080	B
Vest4		0.078
MVP		0.093
MPC		0.94
ClinPred		0.0016	T
GERP RS		-1.2
Varity_R		0.045
gMVP		0.37
Mutation Taster		=100/0	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: rs544558369; hg19: chrX-153069577;