rs363238

Positions:

• chr10-117279248-C-A

Variant summary

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

The NM_173791.5(PDZD8):​c.*4020G>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 0.148 in 151,978 control chromosomes in the GnomAD database, including 1,969 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 0.15 (1969 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: PDZD8 NM_173791.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.196

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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC18A2	NM_003054.6	c.*1982C>A		3_prime_UTR_variant	16/16	ENST00000644641.2	NP_003045.2
PDZD8	NM_173791.5	c.*4020G>T		3_prime_UTR_variant	5/5	ENST00000334464.7	NP_776152.1
PDZD8	XM_005269518.5	c.*4020G>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.*4020G>T		3_prime_UTR_variant	5/5	1	NM_173791.5	ENSP00000334642	P1
SLC18A2	ENST00000644641.2	c.*1982C>A		3_prime_UTR_variant	16/16		NM_003054.6	ENSP00000496339	P1
SLC18A2	ENST00000497497.1	n.3943C>A		non_coding_transcript_exon_variant	15/15	2

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22549 AN: 151860 Hom.: 1965 Cov.: 33

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.207

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.153

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: 0.148 AC: 22568 AN: 151978 Hom.: 1969 Cov.: 33 AF XY: 0.155 AC XY: 11548 AN XY: 74290

Gnomad4 AFR AF: 0.146

Gnomad4 AMR AF: 0.210

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.408

Gnomad4 SAS AF: 0.220

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.151

Alfa AF: 0.129 Hom.: 315

Bravo AF: 0.153

Asia WGS AF: 0.310 AC: 1076 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.3
DANN	Benign	0.52

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: rs363238; hg19: chr10-119038759;