X-153804024-G-C

Variant names:

• chrX-153804024-G-C
• NM_001303512.2:c.1657C>G

Variant summary

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

The NM_001303512.2(PDZD4):​c.1657C>G​(p.Arg553Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000671 in 1,043,676 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: 0.0000067 (0 hom. 1 hem.)
• Consequence: PDZD4 NM_001303512.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.95

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=0.20663905).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDZD4	NM_001303512.2	c.1657C>G	p.Arg553Gly	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.1657C>G	p.Arg553Gly	missense_variant	Exon 8 of 8	1	NM_001303512.2	ENSP00000377355.3
PDZD4	ENST00000164640.8	c.1639C>G	p.Arg547Gly	missense_variant	Exon 8 of 8	1		ENSP00000164640.4
PDZD4	ENST00000544474.5	c.1312C>G	p.Arg438Gly	missense_variant	Exon 6 of 6	1		ENSP00000442033.1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome AF: 0.00000671 AC: 7 AN: 1043676 Hom.: 0 Cov.: 33 AF XY: 0.00000295 AC XY: 1 AN XY: 338560

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: 0.00000734

Gnomad4 OTH exome AF: 0.0000227

GnomAD4 genome Cov.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	16
DANN	Benign	0.87
DEOGEN2	Benign	0.068	T;.;T
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.82	T;T;T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.21	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.81	L;.;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.13	N;N;.
REVEL	Benign	0.13
Sift	Benign	0.19	T;T;.
Sift4G	Benign	0.45	T;T;T
Polyphen		0.079	B;.;B
Vest4		0.32
MutPred		0.22		Loss of solvent accessibility (P = 0.0159);.;.;
MVP		0.24
MPC		1.1
ClinPred		0.12	T
GERP RS		4.6
Varity_R		0.11
gMVP		0.70

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-153069479;