rs782291507

Variant names:

• chrX-153804332-G-A
• rs782291507
• NM_001303512.2:c.1349C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-153804332-G-A
• chrX-153804332-G-C
• chrX-153804332-G-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001303512.2(PDZD4):​c.1349C>T​(p.Ala450Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,092,350 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 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: 0.000017 (0 hom. 10 hem.)
• Consequence: PDZD4 NM_001303512.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0340

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 Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04322177).
• BS2: High Hemizygotes in GnomAdExome4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDZD4	NM_001303512.2	c.1349C>T	p.Ala450Val	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.1349C>T	p.Ala450Val	missense_variant	Exon 8 of 8	1	NM_001303512.2	ENSP00000377355.3
PDZD4	ENST00000164640.8	c.1331C>T	p.Ala444Val	missense_variant	Exon 8 of 8	1		ENSP00000164640.4
PDZD4	ENST00000544474.5	c.1004C>T	p.Ala335Val	missense_variant	Exon 6 of 6	1		ENSP00000442033.1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD3 exomes AF: 0.0000506 AC: 9 AN: 177871 Hom.: 0 AF XY: 0.0000769 AC XY: 5 AN XY: 65057

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000588

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000225

GnomAD4 exome AF: 0.0000174 AC: 19 AN: 1092350 Hom.: 0 Cov.: 33 AF XY: 0.0000278 AC XY: 10 AN XY: 359818

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000431

Gnomad4 SAS exome AF: 0.0000370

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000238

Gnomad4 OTH exome AF: 0.0000435

GnomAD4 genome Cov.: 25

Bravo AF: 0.00000378

ExAC AF: 0.0000495 AC: 6

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.5
DANN	Uncertain	0.98
DEOGEN2	Benign	0.10	T;.;T
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.84	T;T;T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.043	T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.55	N;.;.
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.93	N;N;N
REVEL	Benign	0.039
Sift	Benign	0.064	T;T;T
Sift4G	Benign	0.27	T;T;T
Polyphen		0.0030	B;.;B
Vest4		0.037
MutPred		0.16		Gain of sheet (P = 0.0477);.;.;
MVP		0.16
MPC		1.1
ClinPred		0.016	T
GERP RS		0.94
Varity_R		0.061
gMVP		0.48

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

LitVar

Other links and lift over

dbSNP: rs782291507; hg19: chrX-153069787; COSMIC: COSV51246619; COSMIC: COSV51246619;