chr10-117278157-G-A

Variant names:

• chr10-117278157-G-A
• rs363282
• NM_173791.5:c.*5111C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• brain dopamine-serotonin vesicular transport disease

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, G2P
• parkinsonism-dystonia, infantile, 2

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173791.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDZD8	NM_173791.5	MANE Select	c.*5111C>T		3_prime_UTR	Exon 5 of 5	NP_776152.1
	SLC18A2	NM_003054.6	MANE Select	c.*891G>A		3_prime_UTR	Exon 16 of 16	NP_003045.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDZD8	ENST00000334464.7	TSL:1 MANE Select	c.*5111C>T		3_prime_UTR	Exon 5 of 5	ENSP00000334642.5
	SLC18A2	ENST00000644641.2	MANE Select	c.*891G>A		3_prime_UTR	Exon 16 of 16	ENSP00000496339.1
	SLC18A2	ENST00000497497.1	TSL:2	n.2852G>A		non_coding_transcript_exon	Exon 15 of 15

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.650 AC: 26931 AN: 41452

American (AMR) AF: 0.740 AC: 11304 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.818 AC: 2837 AN: 3470

East Asian (EAS) AF: 0.564 AC: 2911 AN: 5160

South Asian (SAS) AF: 0.740 AC: 3567 AN: 4818

European-Finnish (FIN) AF: 0.841 AC: 8914 AN: 10594

Middle Eastern (MID) AF: 0.748 AC: 217 AN: 290

European-Non Finnish (NFE) AF: 0.849 AC: 57751 AN: 67996

Other (OTH) AF: 0.761 AC: 1609 AN: 2114

Alfa AF: 0.779 Hom.: 7946

Bravo AF: 0.758

Asia WGS AF: 0.635 AC: 2210 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.3
DANN	Benign	0.20
PhyloP100		0.67
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs363282; hg19: chr10-119037668;