10-117307494-T-C

Variant names:

• chr10-117307494-T-C
• rs2803807
• NM_173791.5:c.1098+11378A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173791.5(PDZD8):​c.1098+11378A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.769 in 151,882 control chromosomes in the GnomAD database, including 45,523 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 (45523 hom., cov: 31)
• Consequence: PDZD8 NM_173791.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.672
• Publications: 2 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]

PDZD8 Gene-Disease associations (from GenCC):

• intellectual developmental disorder with autism and dysmorphic facies

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.844 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDZD8	NM_173791.5	c.1098+11378A>G		intron_variant	Intron 3 of 4	ENST00000334464.7	NP_776152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDZD8	ENST00000334464.7	c.1098+11378A>G		intron_variant	Intron 3 of 4	1	NM_173791.5	ENSP00000334642.5
PDZD8	ENST00000482496.5	n.72+6670A>G		intron_variant	Intron 1 of 2	2
PDZD8	ENST00000489302.5	n.107+11378A>G		intron_variant	Intron 1 of 3	3
PDZD8	ENST00000489491.1	n.127-17146A>G		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.769 AC: 116660 AN: 151762 Hom.: 45498 Cov.: 31

Gnomad AFR AF: 0.649

Gnomad AMI AF: 0.914

Gnomad AMR AF: 0.742

Gnomad ASJ AF: 0.817

Gnomad EAS AF: 0.566

Gnomad SAS AF: 0.740

Gnomad FIN AF: 0.841

Gnomad MID AF: 0.745

Gnomad NFE AF: 0.849

Gnomad OTH AF: 0.763

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.769 AC: 116738 AN: 151882 Hom.: 45523 Cov.: 31 AF XY: 0.764 AC XY: 56753 AN XY: 74238

African (AFR) AF: 0.649 AC: 26894 AN: 41410

American (AMR) AF: 0.742 AC: 11315 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.817 AC: 2833 AN: 3466

East Asian (EAS) AF: 0.565 AC: 2919 AN: 5164

South Asian (SAS) AF: 0.739 AC: 3571 AN: 4830

European-Finnish (FIN) AF: 0.841 AC: 8907 AN: 10586

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.849 AC: 57641 AN: 67858

Other (OTH) AF: 0.761 AC: 1603 AN: 2106

Alfa AF: 0.801 Hom.: 6419

Bravo AF: 0.758

Asia WGS AF: 0.633 AC: 2191 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	10
DANN	Benign	0.70
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: rs2803807; hg19: chr10-119067005;