Variant 16-15017355-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015027.4(PDXDC1):c.896C>T(p.Pro299Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,284 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.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 48)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PDXDC1
NM_015027.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.16

Variant links:

Genes affected

PDXDC1 (HGNC:28995): (pyridoxal dependent decarboxylase domain containing 1) Enables cadherin binding activity. Predicted to be involved in carboxylic acid metabolic process. Located in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

PDXDC1 links:

PDXDC1 (HGNC:):

PDXDC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.21313563).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDXDC1	NM_015027.4 linkuse as main transcript	c.896C>T	p.Pro299Leu	missense_variant	11/23	ENST00000396410.9	NP_055842.2	Q6P996-1Q6XYB5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDXDC1	ENST00000396410.9 linkuse as main transcript	c.896C>T	p.Pro299Leu	missense_variant	11/23	1	NM_015027.4	ENSP00000379691.4		Q6P996-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152284

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251476

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000137

AC:

AN:

1461506

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727088

show subpopulations

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152284

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000843

Hom.:

ExAC

AF:

0.00000824

AC:

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

Oct 08, 2024

The c.896C>T (p.P299L) alteration is located in exon 11 (coding exon 11) of the PDXDC1 gene. This alteration results from a C to T substitution at nucleotide position 896, causing the proline (P) at amino acid position 299 to be replaced by a leucine (L). 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

0.095

BayesDel_addAF

Benign

-0.083

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.011

T;T;.;T;.;.;T;T;.

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.079

FATHMM_MKL

Benign

0.60

LIST_S2

Uncertain

0.92

D;.;.;D;D;D;.;D;D

M_CAP

Benign

0.0063

MetaRNN

Benign

0.21

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.72

.;.;.;N;.;.;.;.;.

PrimateAI

Uncertain

0.50

PROVEAN

Benign

0.080

N;N;N;N;N;.;.;N;.

REVEL

Benign

0.20

Sift

Benign

1.0

T;T;T;T;T;.;.;T;.

Sift4G

Benign

1.0

T;T;T;T;T;T;T;T;T

Polyphen

0.17, 0.0020

.;B;B;B;.;.;.;.;.

Vest4

0.40

MutPred

0.78

.;Loss of glycosylation at P299 (P = 0.0425);.;Loss of glycosylation at P299 (P = 0.0425);.;.;Loss of glycosylation at P299 (P = 0.0425);.;.;

MVP

0.33

MPC

0.24

ClinPred

0.32

GERP RS

4.4

Varity_R

0.062

gMVP

0.62

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