10-117277560-T-G

Variant names:

• chr10-117277560-T-G
• rs14240
• NM_173791.5:c.*5708A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173791.5(PDZD8):​c.*5708A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: PDZD8 NM_173791.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.790
• Publications: 13 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: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, PanelApp Australia, Orphanet, G2P
• parkinsonism-dystonia, infantile, 2

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

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDZD8	NM_173791.5	MANE Select	c.*5708A>C		3_prime_UTR	Exon 5 of 5	NP_776152.1	Q8NEN9
	SLC18A2	NM_003054.6	MANE Select	c.*294T>G		3_prime_UTR	Exon 16 of 16	NP_003045.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDZD8	ENST00000334464.7	TSL:1 MANE Select	c.*5708A>C		3_prime_UTR	Exon 5 of 5	ENSP00000334642.5	Q8NEN9
	SLC18A2	ENST00000644641.2	MANE Select	c.*294T>G		3_prime_UTR	Exon 16 of 16	ENSP00000496339.1	Q05940-1
	SLC18A2	ENST00000853677.1		c.*294T>G		3_prime_UTR	Exon 17 of 17	ENSP00000523736.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	15
DANN	Benign	0.81
PhyloP100		0.79

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: rs14240; hg19: chr10-119037071;