Variant 16-15006422-G-A 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.418G>A(p.Glu140Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000652 in 1,595,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 48)

Exomes 𝑓: 0.000055 ( 0 hom. )

Consequence

PDXDC1
NM_015027.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.77

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=0.18408841).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDXDC1	NM_015027.4 linkuse as main transcript	c.418G>A	p.Glu140Lys	missense_variant	6/23	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.418G>A	p.Glu140Lys	missense_variant	6/23	1	NM_015027.4	ENSP00000379691.4		Q6P996-1

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

152294

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000600

AC:

AN:

250056

Hom.:

AF XY:

0.0000740

AC XY:

AN XY:

135164

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000164

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000529

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000554

AC:

AN:

1443414

Hom.:

Cov.:

AF XY:

0.0000448

AC XY:

AN XY:

714486

show subpopulations

Gnomad4 AFR exome

AF:

0.000181

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000637

Gnomad4 OTH exome

AF:

0.0000504

GnomAD4 genome

AF:

0.000157

AC:

AN:

152412

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74538

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000709

Hom.:

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000659

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

Jun 05, 2024

The c.418G>A (p.E140K) alteration is located in exon 6 (coding exon 6) of the PDXDC1 gene. This alteration results from a G to A substitution at nucleotide position 418, causing the glutamic acid (E) at amino acid position 140 to be replaced by a lysine (K). 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

Uncertain

0.37

BayesDel_addAF

Benign

-0.030

BayesDel_noAF

Uncertain

0.030

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.040

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

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.89

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

M_CAP

Benign

0.022

MetaRNN

Benign

0.18

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

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.85

.;.;L;L;.;.;.;.;.

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-2.3

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

REVEL

Benign

0.18

Sift

Benign

0.032

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

Sift4G

Uncertain

0.056

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

Polyphen

0.76, 0.94, 0.63

.;P;P;P;.;.;.;.;.

Vest4

0.80

MVP

0.48

MPC

0.13

ClinPred

0.10

GERP RS

5.8

Varity_R

0.18

gMVP

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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