rs1935168

Positions:

• chr10-117353093-G-A
• chr10-117353093-G-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
PDZD8	NM_173791.5	c.873-11991C>T		intron_variant		ENST00000334464.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDZD8	ENST00000334464.7	c.873-11991C>T		intron_variant		1	NM_173791.5	P1
PDZD8	ENST00000489491.1	n.126+21263C>T		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.681

Gnomad4 AMR AF: 0.466

Gnomad4 ASJ AF: 0.427

Gnomad4 EAS AF: 0.452

Gnomad4 SAS AF: 0.417

Gnomad4 FIN AF: 0.491

Gnomad4 NFE AF: 0.426

Gnomad4 OTH AF: 0.500

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

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

LitVar

Other links and lift over

dbSNP: rs1935168; hg19: chr10-119112604;