GeneBe

10-117279648-A-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_173791.5(PDZD8):​c.*3620T>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 0.217 in 152,108 control chromosomes in the GnomAD database, including 4,046 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 0.22 ( 4046 hom., cov: 33)
Failed GnomAD Quality Control

Consequence

PDZD8
NM_173791.5 3_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.370

Publications

6 publications found
Variant links:
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)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PDZD8NM_173791.5 linkc.*3620T>G 3_prime_UTR_variant Exon 5 of 5 ENST00000334464.7 NP_776152.1 Q8NEN9
PDZD8XM_005269518.5 linkc.*3620T>G 3_prime_UTR_variant Exon 4 of 4 XP_005269575.1
SLC18A2NM_003054.6 linkc.*2382A>C downstream_gene_variant ENST00000644641.2 NP_003045.2 Q05940-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PDZD8ENST00000334464.7 linkc.*3620T>G 3_prime_UTR_variant Exon 5 of 5 1 NM_173791.5 ENSP00000334642.5 Q8NEN9
SLC18A2ENST00000644641.2 linkc.*2382A>C downstream_gene_variant NM_003054.6 ENSP00000496339.1 Q05940-1
SLC18A2ENST00000497497.1 linkn.*218A>C downstream_gene_variant 2

Frequencies

GnomAD3 genomes
AF:
0.218
AC:
33086
AN:
151990
Hom.:
4045
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.133
Gnomad AMI
AF:
0.194
Gnomad AMR
AF:
0.189
Gnomad ASJ
AF:
0.245
Gnomad EAS
AF:
0.0164
Gnomad SAS
AF:
0.161
Gnomad FIN
AF:
0.332
Gnomad MID
AF:
0.329
Gnomad NFE
AF:
0.275
Gnomad OTH
AF:
0.227
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AC:
0
AN:
0
Hom.:
0
Cov.:
0
AC XY:
0
AN XY:
0
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)
AC:
0
AN:
0
Other (OTH)
AC:
0
AN:
0
GnomAD4 genome
AF:
0.217
AC:
33083
AN:
152108
Hom.:
4046
Cov.:
33
AF XY:
0.217
AC XY:
16109
AN XY:
74344
show subpopulations
African (AFR)
AF:
0.133
AC:
5527
AN:
41518
American (AMR)
AF:
0.188
AC:
2875
AN:
15280
Ashkenazi Jewish (ASJ)
AF:
0.245
AC:
850
AN:
3468
East Asian (EAS)
AF:
0.0164
AC:
85
AN:
5170
South Asian (SAS)
AF:
0.161
AC:
775
AN:
4824
European-Finnish (FIN)
AF:
0.332
AC:
3501
AN:
10556
Middle Eastern (MID)
AF:
0.340
AC:
100
AN:
294
European-Non Finnish (NFE)
AF:
0.275
AC:
18719
AN:
67976
Other (OTH)
AF:
0.225
AC:
474
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
1286
2572
3857
5143
6429
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
348
696
1044
1392
1740
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.254
Hom.:
710
Bravo
AF:
0.201
Asia WGS
AF:
0.0900
AC:
313
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
CADD
Benign
0.30
DANN
Benign
0.60
PhyloP100
-0.37

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

Other links and lift over

dbSNP: rs363285; hg19: chr10-119039159; API