10-117284532-AAACT-A

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_Strong PM2 PP5

The NM_173791.5(PDZD8):c.2197_2200del(p.Ser733Ter) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PDZD8 NM_173791.5 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 8.02

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 Likely_pathogenic. Variant got 7 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.366 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 10-117284532-AAACT-A is Pathogenic according to our data. Variant chr10-117284532-AAACT-A is described in ClinVar as [Pathogenic]. Clinvar id is 1703715.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDZD8	NM_173791.5	c.2197_2200del	p.Ser733Ter	frameshift_variant	5/5	ENST00000334464.7
PDZD8	XM_005269518.5	c.2074_2077del	p.Ser692Ter	frameshift_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDZD8	ENST00000334464.7	c.2197_2200del	p.Ser733Ter	frameshift_variant	5/5	1	NM_173791.5	P1
PDZD8	ENST00000482496.5	n.1171_1174del		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Intellectual developmental disorder with autism and dysmorphic facies Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Aug 31, 2022

- -

Computational scores

Source: dbNSFP v4.3

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-119044043;