rs363282

Positions:

• chr10-117278157-G-A
• chr10-117278157-G-C
• chr10-117278157-G-T

Variant summary

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

The NM_173791.5(PDZD8):​c.*5111C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.769 in 152,076 control chromosomes in the GnomAD database, including 45,571 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 0.77 (45570 hom., cov: 32)
  • Exomes 𝑓: 1.0 (1 hom.)
• Consequence: PDZD8 NM_173791.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.673

Genes affected

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]

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 = 0.844 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC18A2	NM_003054.6	c.*891G>A		3_prime_UTR_variant	16/16	ENST00000644641.2	NP_003045.2
PDZD8	NM_173791.5	c.*5111C>T		3_prime_UTR_variant	5/5	ENST00000334464.7	NP_776152.1
PDZD8	XM_005269518.5	c.*5111C>T		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.*5111C>T		3_prime_UTR_variant	5/5	1	NM_173791.5	ENSP00000334642	P1
SLC18A2	ENST00000644641.2	c.*891G>A		3_prime_UTR_variant	16/16		NM_003054.6	ENSP00000496339	P1
SLC18A2	ENST00000497497.1	n.2852G>A		non_coding_transcript_exon_variant	15/15	2

Frequencies

GnomAD3 genomes AF: 0.769 AC: 116797 AN: 151956 Hom.: 45544 Cov.: 32

Gnomad AFR AF: 0.649

Gnomad AMI AF: 0.914

Gnomad AMR AF: 0.741

Gnomad ASJ AF: 0.818

Gnomad EAS AF: 0.565

Gnomad SAS AF: 0.741

Gnomad FIN AF: 0.841

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.849

Gnomad OTH AF: 0.762

GnomAD4 exome AF: 1.00 AC: 2 AN: 2 Hom.: 1 Cov.: 0 AF XY: 1.00 AC XY: 2 AN XY: 2

Gnomad4 NFE exome AF: 1.00

GnomAD4 genome AF: 0.769 AC: 116875 AN: 152074 Hom.: 45570 Cov.: 32 AF XY: 0.764 AC XY: 56848 AN XY: 74368

Gnomad4 AFR AF: 0.650

Gnomad4 AMR AF: 0.740

Gnomad4 ASJ AF: 0.818

Gnomad4 EAS AF: 0.564

Gnomad4 SAS AF: 0.740

Gnomad4 FIN AF: 0.841

Gnomad4 NFE AF: 0.849

Gnomad4 OTH AF: 0.761

Alfa AF: 0.783 Hom.: 7782

Bravo AF: 0.758

Asia WGS AF: 0.635 AC: 2210 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.3
DANN	Benign	0.20

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: rs363282; hg19: chr10-119037668;