10-117307494-T-C

Position:

• chr10-117307494-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.8).
• 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/exons	MANE	Protein	UniProt
PDZD8	NM_173791.5	c.1098+11378A>G		intron_variant		ENST00000334464.7	NP_776152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDZD8	ENST00000334464.7	c.1098+11378A>G		intron_variant		1	NM_173791.5	ENSP00000334642	P1
PDZD8	ENST00000482496.5	n.72+6670A>G		intron_variant, non_coding_transcript_variant		2
PDZD8	ENST00000489302.5	n.107+11378A>G		intron_variant, non_coding_transcript_variant		3
PDZD8	ENST00000489491.1	n.127-17146A>G		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.649

Gnomad4 AMR AF: 0.742

Gnomad4 ASJ AF: 0.817

Gnomad4 EAS AF: 0.565

Gnomad4 SAS AF: 0.739

Gnomad4 FIN AF: 0.841

Gnomad4 NFE AF: 0.849

Gnomad4 OTH AF: 0.761

Alfa AF: 0.807 Hom.: 6255

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

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: rs2803807; hg19: chr10-119067005;