chrX-153804171-C-A

Variant names:

• chrX-153804171-C-A
• NM_001303512.2:c.1510G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001303512.2(PDZD4):​c.1510G>T​(p.Gly504Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000094 in 1,063,400 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 9.4e-7 (0 hom. 1 hem.)
• Consequence: PDZD4 NM_001303512.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.112

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1340552).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDZD4	NM_001303512.2	c.1510G>T	p.Gly504Cys	missense_variant	Exon 8 of 8	ENST00000393758.7	NP_001290441.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDZD4	ENST00000393758.7	c.1510G>T	p.Gly504Cys	missense_variant	Exon 8 of 8	1	NM_001303512.2	ENSP00000377355.3
PDZD4	ENST00000164640.8	c.1492G>T	p.Gly498Cys	missense_variant	Exon 8 of 8	1		ENSP00000164640.4
PDZD4	ENST00000544474.5	c.1165G>T	p.Gly389Cys	missense_variant	Exon 6 of 6	1		ENSP00000442033.1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome AF: 9.40e-7 AC: 1 AN: 1063400 Hom.: 0 Cov.: 33 AF XY: 0.00000292 AC XY: 1 AN XY: 342244

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000121

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T;.;T
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.79	T;T;T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;.;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.7	N;N;.
REVEL	Benign	0.098
Sift	Benign	0.14	T;T;.
Sift4G	Uncertain	0.0080	D;D;D
Polyphen		0.99	D;.;D
Vest4		0.28
MutPred		0.29		Gain of catalytic residue at M496 (P = 5e-04);.;.;
MVP		0.25
MPC		1.7
ClinPred		0.45	T
GERP RS		4.1
Varity_R		0.20
gMVP		0.57

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-153069626;