10-117277498-A-C

Position:

• chr10-117277498-A-C

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_173791.5(PDZD8):​c.*5770T>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 0.496 in 269,082 control chromosomes in the GnomAD database, including 34,016 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.46 (16501 hom., cov: 33)
  • Exomes 𝑓: 0.55 (17515 hom.)
• Consequence: PDZD8 NM_173791.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.82

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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 10-117277498-A-C is Benign according to our data. Variant chr10-117277498-A-C is described in ClinVar as [Benign]. Clinvar id is 1175418.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.*5770T>G		3_prime_UTR_variant	5/5	ENST00000334464.7	NP_776152.1
SLC18A2	NM_003054.6	c.*232A>C		3_prime_UTR_variant	16/16	ENST00000644641.2	NP_003045.2
PDZD8	XM_005269518.5	c.*5770T>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.*5770T>G		3_prime_UTR_variant	5/5	1	NM_173791.5	ENSP00000334642.5
SLC18A2	ENST00000644641.2	c.*232A>C		3_prime_UTR_variant	16/16		NM_003054.6	ENSP00000496339.1
SLC18A2	ENST00000497497.1	n.2193A>C		non_coding_transcript_exon_variant	15/15	2

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69285 AN: 152014 Hom.: 16504 Cov.: 33

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.714

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.461

Gnomad EAS AF: 0.539

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.454

GnomAD4 exome AF: 0.548 AC: 64055 AN: 116952 Hom.: 17515 Cov.: 2 AF XY: 0.548 AC XY: 32764 AN XY: 59778

Gnomad4 AFR exome AF: 0.349

Gnomad4 AMR exome AF: 0.619

Gnomad4 ASJ exome AF: 0.491

Gnomad4 EAS exome AF: 0.589

Gnomad4 SAS exome AF: 0.567

Gnomad4 FIN exome AF: 0.549

Gnomad4 NFE exome AF: 0.552

Gnomad4 OTH exome AF: 0.549

GnomAD4 genome AF: 0.455 AC: 69294 AN: 152130 Hom.: 16501 Cov.: 33 AF XY: 0.455 AC XY: 33833 AN XY: 74376

Gnomad4 AFR AF: 0.310

Gnomad4 AMR AF: 0.508

Gnomad4 ASJ AF: 0.461

Gnomad4 EAS AF: 0.538

Gnomad4 SAS AF: 0.498

Gnomad4 FIN AF: 0.474

Gnomad4 NFE AF: 0.517

Gnomad4 OTH AF: 0.449

Alfa AF: 0.459 Hom.: 2452

Bravo AF: 0.457

Asia WGS AF: 0.487 AC: 1682 AN: 3458

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 14, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	16
DANN	Benign	0.84

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: rs10377; hg19: chr10-119037009; COSMIC: COSV53690199;