10-117277560-T-C

Position:

• chr10-117277560-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_173791.5(PDZD8):​c.*5708A>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 0.469 in 174,540 control chromosomes in the GnomAD database, including 20,079 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 0.46 (16476 hom., cov: 33)
  • Exomes 𝑓: 0.56 (3603 hom.)
• Consequence: PDZD8 NM_173791.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.790

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]

SLC18A2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDZD8	NM_173791.5	c.*5708A>G		3_prime_UTR_variant	5/5	ENST00000334464.7	NP_776152.1
SLC18A2	NM_003054.6	c.*294T>C		3_prime_UTR_variant	16/16	ENST00000644641.2	NP_003045.2
PDZD8	XM_005269518.5	c.*5708A>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	c.*5708A>G		3_prime_UTR_variant	5/5	1	NM_173791.5	ENSP00000334642.5
SLC18A2	ENST00000644641.2	c.*294T>C		3_prime_UTR_variant	16/16		NM_003054.6	ENSP00000496339.1
SLC18A2	ENST00000497497.1	n.2255T>C		non_coding_transcript_exon_variant	15/15	2

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69216 AN: 151936 Hom.: 16479 Cov.: 33

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.714

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.538

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.454

GnomAD4 exome AF: 0.563 AC: 12651 AN: 22486 Hom.: 3603 Cov.: 0 AF XY: 0.559 AC XY: 6505 AN XY: 11646

Gnomad4 AFR exome AF: 0.371

Gnomad4 AMR exome AF: 0.591

Gnomad4 ASJ exome AF: 0.515

Gnomad4 EAS exome AF: 0.602

Gnomad4 SAS exome AF: 0.569

Gnomad4 FIN exome AF: 0.552

Gnomad4 NFE exome AF: 0.570

Gnomad4 OTH exome AF: 0.590

GnomAD4 genome AF: 0.455 AC: 69225 AN: 152054 Hom.: 16476 Cov.: 33 AF XY: 0.455 AC XY: 33808 AN XY: 74344

Gnomad4 AFR AF: 0.309

Gnomad4 AMR AF: 0.508

Gnomad4 ASJ AF: 0.460

Gnomad4 EAS AF: 0.538

Gnomad4 SAS AF: 0.498

Gnomad4 FIN AF: 0.475

Gnomad4 NFE AF: 0.517

Gnomad4 OTH AF: 0.449

Alfa AF: 0.448 Hom.: 3016

Bravo AF: 0.457

Asia WGS AF: 0.483 AC: 1674 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	16
DANN	Benign	0.83

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: rs14240; hg19: chr10-119037071;