chr16-21984272-C-A

Position:

• chr16-21984272-C-A

Variant summary

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

The NM_001363519.1(PDZD9):​c.790G>T​(p.Gly264Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PDZD9 NM_001363519.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.00400

Genes affected

PDZD9 (HGNC:28740): (PDZ domain containing 9)

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=0.12721446).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDZD9	NM_001363519.1	c.790G>T	p.Gly264Cys	missense_variant	4/4	ENST00000424898.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDZD9	ENST00000424898.3	c.790G>T	p.Gly264Cys	missense_variant	4/4	5	NM_001363519.1	P1
PDZD9	ENST00000523914.5	c.*567G>T		3_prime_UTR_variant, NMD_transcript_variant	5/5	1
PDZD9	ENST00000537222.6	c.610G>T	p.Gly204Cys	missense_variant	3/3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 17, 2023

The c.610G>T (p.G204C) alteration is located in exon 3 (coding exon 3) of the PDZD9 gene. This alteration results from a G to T substitution at nucleotide position 610, causing the glycine (G) at amino acid position 204 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.030	.;T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.27	N
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.4	.;L
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.31	T
PROVEAN	Pathogenic	-4.6	D;D
REVEL	Benign	0.046
Sift	Uncertain	0.0050	D;D
Sift4G	Pathogenic	0.0	D;D
Vest4		0.34
MutPred		0.32		.;Loss of ubiquitination at K262 (P = 0.0525);
MVP		0.24
MPC		1.0
ClinPred		0.82	D
GERP RS		2.6
Varity_R		0.20
gMVP		0.033

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: rs944979169; hg19: chr16-21995593;