X-153803400-C-T

Variant names:

• chrX-153803400-C-T
• rs2092187313
• NM_001303512.2:c.2281G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001303512.2(PDZD4):​c.2281G>A​(p.Asp761Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000292 in 1,028,431 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D761Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 0.0000029 (0 hom. 1 hem.)
• Consequence: PDZD4 NM_001303512.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.13
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.2281G>A	p.Asp761Asn	missense	Exon 8 of 8	NP_001290441.1	Q17RL8
	PDZD4	NM_032512.5		c.2263G>A	p.Asp755Asn	missense	Exon 8 of 8	NP_115901.2
	PDZD4	NM_001303515.2		c.2038G>A	p.Asp680Asn	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.2281G>A	p.Asp761Asn	missense	Exon 8 of 8	ENSP00000377355.3	Q17RL8
	PDZD4	ENST00000164640.8	TSL:1	c.2263G>A	p.Asp755Asn	missense	Exon 8 of 8	ENSP00000164640.4	Q76G19-1
	PDZD4	ENST00000544474.5	TSL:1	c.1936G>A	p.Asp646Asn	missense	Exon 6 of 6	ENSP00000442033.1	Q76G19-2

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome AF: 0.00000292 AC: 3 AN: 1028431 Hom.: 0 Cov.: 32 AF XY: 0.00000302 AC XY: 1 AN XY: 331163

African (AFR) AF: 0.00 AC: 0 AN: 23701

American (AMR) AF: 0.00 AC: 0 AN: 22879

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14875

East Asian (EAS) AF: 0.0000338 AC: 1 AN: 29544

South Asian (SAS) AF: 0.00 AC: 0 AN: 44328

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36127

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3787

European-Non Finnish (NFE) AF: 0.00000123 AC: 1 AN: 810220

Other (OTH) AF: 0.0000233 AC: 1 AN: 42970

GnomAD4 genome Cov.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.58	D
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Pathogenic	0.42	D
MetaRNN	Uncertain	0.47	T
MetaSVM	Uncertain	0.26	D
MutationAssessor	Uncertain	2.4	M
PhyloP100		6.1
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-3.9	D
REVEL	Uncertain	0.47
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.35
MutPred		0.42		Gain of MoRF binding (P = 0.0301)
MVP		0.88
MPC		2.0
ClinPred		0.98	D
GERP RS		5.6
Varity_R		0.65
gMVP		0.92
Mutation Taster		=58/42	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: rs2092187313; hg19: chrX-153068855; COSMIC: COSV51248477; COSMIC: COSV51248477;