16-21984317-A-C

Position:

• chr16-21984317-A-C

Variant summary

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

The NM_001363519.1(PDZD9):​c.745T>G​(p.Cys249Gly) 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: 2.13

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=0.11643037).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDZD9	NM_001363519.1	c.745T>G	p.Cys249Gly	missense_variant	4/4	ENST00000424898.3	NP_001350448.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDZD9	ENST00000424898.3	c.745T>G	p.Cys249Gly	missense_variant	4/4	5	NM_001363519.1	ENSP00000400514	P1
PDZD9	ENST00000523914.5	c.*522T>G		3_prime_UTR_variant, NMD_transcript_variant	5/5	1		ENSP00000429211
PDZD9	ENST00000537222.6	c.565T>G	p.Cys189Gly	missense_variant	3/3	3		ENSP00000441685

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

Sep 15, 2021

The c.565T>G (p.C189G) alteration is located in exon 3 (coding exon 3) of the PDZD9 gene. This alteration results from a T to G substitution at nucleotide position 565, causing the cysteine (C) at amino acid position 189 to be replaced by a glycine (G). 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	0.12
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	17
DANN	Benign	0.95
DEOGEN2	Benign	0.10	.;T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.63	D
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	.;L
MutationTaster	Benign	0.99	N;N;N
PrimateAI	Benign	0.25	T
PROVEAN	Pathogenic	-4.8	D;D
REVEL	Benign	0.13
Sift	Uncertain	0.010	D;D
Sift4G	Uncertain	0.020	D;D
Vest4		0.10
MutPred		0.54		.;Gain of disorder (P = 0.0149);
MVP		0.26
MPC		0.37
ClinPred		0.77	D
GERP RS		4.2
Varity_R		0.37
gMVP		0.026

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: chr16-21995638;