X-153804122-G-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_001303512.2(PDZD4):​c.1559C>A​(p.Pro520His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00002 in 1,150,583 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P520R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000088 (0 hom., 0 hem., cov: 26)
  • Exomes 𝑓: 0.000021 (0 hom. 8 hem.)
• Consequence: PDZD4 NM_001303512.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B: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=0.08765218).
• BP6: Variant X-153804122-G-T is Benign according to our data. Variant chrX-153804122-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3305656.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAdExome4 at 8 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>A	p.Pro520His	missense	Exon 8 of 8	NP_001290441.1	Q17RL8
	PDZD4	NM_032512.5		c.1541C>A	p.Pro514His	missense	Exon 8 of 8	NP_115901.2
	PDZD4	NM_001303515.2		c.1316C>A	p.Pro439His	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>A	p.Pro520His	missense	Exon 8 of 8	ENSP00000377355.3	Q17RL8
	PDZD4	ENST00000164640.8	TSL:1	c.1541C>A	p.Pro514His	missense	Exon 8 of 8	ENSP00000164640.4	Q76G19-1
	PDZD4	ENST00000544474.5	TSL:1	c.1214C>A	p.Pro405His	missense	Exon 6 of 6	ENSP00000442033.1	Q76G19-2

Frequencies

GnomAD3 genomes AF: 0.00000882 AC: 1 AN: 113393 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000187

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 88205 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.0000212 AC: 22 AN: 1037190 Hom.: 0 Cov.: 33 AF XY: 0.0000239 AC XY: 8 AN XY: 334308

African (AFR) AF: 0.00 AC: 0 AN: 24823

American (AMR) AF: 0.00 AC: 0 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: 29098

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3708

European-Non Finnish (NFE) AF: 0.0000258 AC: 21 AN: 815208

Other (OTH) AF: 0.0000228 AC: 1 AN: 43879

GnomAD4 genome AF: 0.00000882 AC: 1 AN: 113393 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 35539

African (AFR) AF: 0.00 AC: 0 AN: 31286

American (AMR) AF: 0.00 AC: 0 AN: 10891

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 3567

South Asian (SAS) AF: 0.00 AC: 0 AN: 2842

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 237

European-Non Finnish (NFE) AF: 0.0000187 AC: 1 AN: 53336

Other (OTH) AF: 0.00 AC: 0 AN: 1537

Alfa AF: 0.00 Hom.: 2

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.094
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-1.1
CADD	Benign	2.5
DANN	Benign	0.64
DEOGEN2	Benign	0.11	T
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.62
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.38	N
REVEL	Benign	0.014
Sift	Benign	0.19	T
Sift4G	Uncertain	0.056	T
Polyphen		0.0	B
Vest4		0.066
MutPred		0.15		Loss of glycosylation at P514 (P = 0.0308)
MVP		0.068
MPC		1.0
ClinPred		0.11	T
GERP RS		-1.2
Varity_R		0.083
gMVP		0.28
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: rs544558369; hg19: chrX-153069577;