Variant 16-21984571-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001363519.1(PDZD9):c.491A>G(p.Tyr164Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000248 in 1,572,988 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

PDZD9
NM_001363519.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.930

Variant links:

Genes affected

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

PDZD9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.40264916).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDZD9	NM_001363519.1 linkuse as main transcript	c.491A>G	p.Tyr164Cys	missense_variant	4/4	ENST00000424898.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDZD9	ENST00000424898.3 linkuse as main transcript	c.491A>G	p.Tyr164Cys	missense_variant	4/4	5	NM_001363519.1	P1	Q8IXQ8-1
PDZD9	ENST00000523914.5 linkuse as main transcript	c.*268A>G		3_prime_UTR_variant, NMD_transcript_variant	5/5	1
PDZD9	ENST00000537222.6 linkuse as main transcript	c.311A>G	p.Tyr104Cys	missense_variant	3/3	3			Q8IXQ8-3

Frequencies

GnomAD3 genomes

AF:

0.0000788

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00000424

AC:

AN:

235808

Hom.:

AF XY:

0.00

AC XY:

AN XY:

127318

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000572

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000155

AC:

AN:

1420646

Hom.:

Cov.:

AF XY:

0.0000129

AC XY:

AN XY:

699286

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000247

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000258

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000460

Gnomad4 OTH exome

AF:

0.000256

GnomAD4 genome

AF:

0.000112

AC:

AN:

152342

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00378

Bravo

AF:

0.0000264

ExAC

AF:

0.0000165

AC:

Asia WGS

AF:

0.00693

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 07, 2023

The c.311A>G (p.Y104C) alteration is located in exon 3 (coding exon 3) of the PDZD9 gene. This alteration results from a A to G substitution at nucleotide position 311, causing the tyrosine (Y) at amino acid position 104 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

0.14

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.12

.;T

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.32

FATHMM_MKL

Benign

0.36

M_CAP

Benign

0.028

MetaRNN

Benign

0.40

T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

1.9

.;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.51

PROVEAN

Pathogenic

-6.7

D;N

REVEL

Benign

0.15

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.0040

D;D

Vest4

0.52

MutPred

0.46

.;Loss of methylation at K160 (P = 0.0674);

MVP

0.58

MPC

1.1

ClinPred

0.59

GERP RS

1.7

Varity_R

0.13

gMVP

0.25

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over