chrX-153804167-T-C

Variant names:

• chrX-153804167-T-C
• rs368385447
• NM_001303512.2:c.1514A>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.1514A>G​(p.Asn505Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00043 in 1,172,612 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 160 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., 4 hem., cov: 25)
  • Exomes 𝑓: 0.00046 (0 hom. 156 hem.)
• Consequence: PDZD4 NM_001303512.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.81
• 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=0.017238766).
• BS2: High Hemizygotes in GnomAd4 at 4 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.1514A>G	p.Asn505Ser	missense	Exon 8 of 8	NP_001290441.1
	PDZD4	NM_032512.5		c.1496A>G	p.Asn499Ser	missense	Exon 8 of 8	NP_115901.2
	PDZD4	NM_001303515.2		c.1271A>G	p.Asn424Ser	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.1514A>G	p.Asn505Ser	missense	Exon 8 of 8	ENSP00000377355.3
	PDZD4	ENST00000164640.8	TSL:1	c.1496A>G	p.Asn499Ser	missense	Exon 8 of 8	ENSP00000164640.4
	PDZD4	ENST00000544474.5	TSL:1	c.1169A>G	p.Asn390Ser	missense	Exon 6 of 6	ENSP00000442033.1

Frequencies

GnomAD3 genomes AF: 0.000142 AC: 16 AN: 112291 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.0000323

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: 0.000323

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000245

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000116 AC: 14 AN: 120375 AF XY: 0.0000917

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: 0.000339

Gnomad NFE exome AF: 0.000224

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000460 AC: 488 AN: 1060270 Hom.: 0 Cov.: 33 AF XY: 0.000458 AC XY: 156 AN XY: 340770

African (AFR) AF: 0.00 AC: 0 AN: 25658

American (AMR) AF: 0.0000329 AC: 1 AN: 30383

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18519

East Asian (EAS) AF: 0.00 AC: 0 AN: 28562

South Asian (SAS) AF: 0.00 AC: 0 AN: 50762

European-Finnish (FIN) AF: 0.000178 AC: 6 AN: 33714

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3604

European-Non Finnish (NFE) AF: 0.000573 AC: 472 AN: 824417

Other (OTH) AF: 0.000202 AC: 9 AN: 44651

GnomAD4 genome AF: 0.000142 AC: 16 AN: 112342 Hom.: 0 Cov.: 25 AF XY: 0.000116 AC XY: 4 AN XY: 34620

African (AFR) AF: 0.0000322 AC: 1 AN: 31021

American (AMR) AF: 0.00 AC: 0 AN: 10787

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2645

East Asian (EAS) AF: 0.00 AC: 0 AN: 3518

South Asian (SAS) AF: 0.00 AC: 0 AN: 2755

European-Finnish (FIN) AF: 0.000323 AC: 2 AN: 6196

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 216

European-Non Finnish (NFE) AF: 0.000245 AC: 13 AN: 52999

Other (OTH) AF: 0.00 AC: 0 AN: 1534

Alfa AF: 0.000285 Hom.: 1

Bravo AF: 0.000136

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000459 AC: 3

ExAC AF: 0.000120 AC: 14

ClinVar

ClinVar submissions as Germline

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	0.085
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.91
CADD	Benign	15
DANN	Benign	0.32
DEOGEN2	Benign	0.068	T
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.017	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.60	N
PhyloP100		1.8
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.040	N
REVEL	Benign	0.11
Sift	Benign	0.96	T
Sift4G	Benign	0.93	T
Polyphen		0.26	B
Vest4		0.14
MVP		0.40
MPC		0.74
ClinPred		0.057	T
GERP RS		5.3
Varity_R		0.056
gMVP		0.15
Mutation Taster		=98/2	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: rs368385447; hg19: chrX-153069622;