rs363285

Positions:

• chr10-117279648-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173791.5(PDZD8):​c.*3620T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 152,108 control chromosomes in the GnomAD database, including 4,046 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.22 (4046 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: PDZD8 NM_173791.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.370

Genes affected

PDZD8 (HGNC:26974): (PDZ domain containing 8) Predicted to enable lipid binding activity and metal ion binding activity. Involved in several processes, including mitochondrial calcium ion homeostasis; mitochondrion-endoplasmic reticulum membrane tethering; and regulation of cell morphogenesis. Located in endoplasmic reticulum membrane and mitochondria-associated endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDZD8	NM_173791.5	c.*3620T>G		3_prime_UTR_variant	5/5	ENST00000334464.7	NP_776152.1
PDZD8	XM_005269518.5	c.*3620T>G		3_prime_UTR_variant	4/4		XP_005269575.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDZD8	ENST00000334464.7	c.*3620T>G		3_prime_UTR_variant	5/5	1	NM_173791.5	ENSP00000334642	P1

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33086 AN: 151990 Hom.: 4045 Cov.: 33

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.0164

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.227

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.217 AC: 33083 AN: 152108 Hom.: 4046 Cov.: 33 AF XY: 0.217 AC XY: 16109 AN XY: 74344

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.188

Gnomad4 ASJ AF: 0.245

Gnomad4 EAS AF: 0.0164

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.332

Gnomad4 NFE AF: 0.275

Gnomad4 OTH AF: 0.225

Alfa AF: 0.258 Hom.: 699

Bravo AF: 0.201

Asia WGS AF: 0.0900 AC: 313 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.30
DANN	Benign	0.60

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: rs363285; hg19: chr10-119039159;