rs363285

Variant names:

• chr10-117279648-A-C
• rs363285
• NM_173791.5:c.*3620T>G

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]

SLC18A2 (HGNC:10935): (solute carrier family 18 member A2) This gene encodes an transmembrane protein that functions as an ATP-dependent transporter of monoamines, such as dopamine, norepinephrine, serotonin, and histamine. This protein transports amine neurotransmitters into synaptic vesicles. Polymorphisms in this gene may be associated with schizophrenia, bipolar disorder, and other neurological/psychiatric ailments. [provided by RefSeq, Jun 2018]

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 rank	MANE	Protein	UniProt
PDZD8	NM_173791.5	c.*3620T>G		3_prime_UTR_variant	Exon 5 of 5	ENST00000334464.7	NP_776152.1
PDZD8	XM_005269518.5	c.*3620T>G		3_prime_UTR_variant	Exon 4 of 4		XP_005269575.1
SLC18A2	NM_003054.6	c.*2382A>C		downstream_gene_variant		ENST00000644641.2	NP_003045.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDZD8	ENST00000334464	c.*3620T>G		3_prime_UTR_variant	Exon 5 of 5	1	NM_173791.5	ENSP00000334642.5
SLC18A2	ENST00000644641.2	c.*2382A>C		downstream_gene_variant			NM_003054.6	ENSP00000496339.1
SLC18A2	ENST00000497497.1	n.*218A>C		downstream_gene_variant		2

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;