rs363294

Variant names:

• chr10-117284043-C-G
• NM_173791.5:c.2690G>C

Your query was ambiguous. Multiple possible variants found:

• chr10-117284043-C-G
• chr10-117284043-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173791.5(PDZD8):​c.2690G>C​(p.Arg897Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R897Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: PDZD8 NM_173791.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.870

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09643513).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDZD8	NM_173791.5	c.2690G>C	p.Arg897Pro	missense_variant	Exon 5 of 5	ENST00000334464.7	NP_776152.1
PDZD8	XM_005269518.5	c.2567G>C	p.Arg856Pro	missense_variant	Exon 4 of 4		XP_005269575.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDZD8	ENST00000334464.7	c.2690G>C	p.Arg897Pro	missense_variant	Exon 5 of 5	1	NM_173791.5	ENSP00000334642.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461858 Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2 AN XY: 727224

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.063	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	17
DANN	Benign	0.95
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-0.55	T
MutationAssessor	Benign	0.46	N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.65	N
REVEL	Uncertain	0.48
Sift	Benign	0.094	T
Sift4G	Uncertain	0.0080	D
Polyphen		0.0020	B
Vest4		0.22
MutPred		0.51		Loss of MoRF binding (P = 0.0085);
MVP		0.83
MPC		0.32
ClinPred		0.12	T
GERP RS		1.7
Varity_R		0.29
gMVP		0.83

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: chr10-119043554;