chr10-117353093-G-A

Variant names:

• chr10-117353093-G-A
• rs1935168
• NM_173791.5:c.873-11991C>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.873-11991C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 152,022 control chromosomes in the GnomAD database, including 20,395 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 0.51 (20395 hom., cov: 32)
• Consequence: PDZD8 NM_173791.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0350
• Publications: 0 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.674 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDZD8	NM_173791.5	c.873-11991C>T		intron_variant	Intron 1 of 4	ENST00000334464.7	NP_776152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDZD8	ENST00000334464.7	c.873-11991C>T		intron_variant	Intron 1 of 4	1	NM_173791.5	ENSP00000334642.5
PDZD8	ENST00000489491.1	n.126+21263C>T		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.505 AC: 76691 AN: 151904 Hom.: 20358 Cov.: 32

Gnomad AFR AF: 0.681

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.502

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

GnomAD4 genome AF: 0.505 AC: 76784 AN: 152022 Hom.: 20395 Cov.: 32 AF XY: 0.506 AC XY: 37613 AN XY: 74312

African (AFR) AF: 0.681 AC: 28226 AN: 41450

American (AMR) AF: 0.466 AC: 7111 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 1483 AN: 3470

East Asian (EAS) AF: 0.452 AC: 2338 AN: 5172

South Asian (SAS) AF: 0.417 AC: 2013 AN: 4830

European-Finnish (FIN) AF: 0.491 AC: 5187 AN: 10556

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.426 AC: 28941 AN: 67956

Other (OTH) AF: 0.500 AC: 1054 AN: 2106

Alfa AF: 0.485 Hom.: 2321

Bravo AF: 0.507

Asia WGS AF: 0.464 AC: 1613 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	7.1
DANN	Benign	0.51
PhyloP100		-0.035
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: rs1935168; hg19: chr10-119112604;