Genetic Variant PDXDC1:p.Ile82Met (chr16-15004190-C-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015027.4(PDXDC1):c.246C>G(p.Ile82Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 1,452,812 control chromosomes in the GnomAD database, including 18,691 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 1917 hom., cov: 51)

Exomes 𝑓: 0.25 ( 16774 hom. )

Consequence

PDXDC1
NM_015027.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.86

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016328692).

BP6

Variant 16-15004190-C-G is Benign according to our data. Variant chr16-15004190-C-G is described in ClinVar as [Benign]. Clinvar id is 768753.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDXDC1	NM_015027.4 link	c.246C>G	p.Ile82Met	missense_variant	Exon 5 of 23	ENST00000396410.9	NP_055842.2	Q6P996-1Q6XYB5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDXDC1	ENST00000396410.9 link	c.246C>G	p.Ile82Met	missense_variant	Exon 5 of 23	1	NM_015027.4	ENSP00000379691.4		Q6P996-1

Frequencies

GnomAD3 genomes

AF:

0.250

AC:

36517

AN:

145896

Hom.:

1901

Cov.:

show subpopulations

Gnomad AFR

AF:

0.166

Gnomad AMI

AF:

0.200

Gnomad AMR

AF:

0.364

Gnomad ASJ

AF:

0.270

Gnomad EAS

AF:

0.448

Gnomad SAS

AF:

0.356

Gnomad FIN

AF:

0.290

Gnomad MID

AF:

0.192

Gnomad NFE

AF:

0.248

Gnomad OTH

AF:

0.258

GnomAD3 exomes

AF:

0.303

AC:

72679

AN:

239652

Hom.:

6576

AF XY:

0.298

AC XY:

38619

AN XY:

129484

show subpopulations

Gnomad AFR exome

AF:

0.159

Gnomad AMR exome

AF:

0.470

Gnomad ASJ exome

AF:

0.275

Gnomad EAS exome

AF:

0.464

Gnomad SAS exome

AF:

0.341

Gnomad FIN exome

AF:

0.285

Gnomad NFE exome

AF:

0.242

Gnomad OTH exome

AF:

0.274

GnomAD4 exome

AF:

0.246

AC:

322105

AN:

1306792

Hom.:

16774

Cov.:

AF XY:

0.250

AC XY:

163094

AN XY:

653256

show subpopulations

Gnomad4 AFR exome

AF:

0.156

Gnomad4 AMR exome

AF:

0.460

Gnomad4 ASJ exome

AF:

0.268

Gnomad4 EAS exome

AF:

0.511

Gnomad4 SAS exome

AF:

0.334

Gnomad4 FIN exome

AF:

0.279

Gnomad4 NFE exome

AF:

0.219

Gnomad4 OTH exome

AF:

0.257

GnomAD4 genome

AF:

0.250

AC:

36577

AN:

146020

Hom.:

1917

Cov.:

AF XY:

0.257

AC XY:

18342

AN XY:

71416

show subpopulations

Gnomad4 AFR

AF:

0.166

Gnomad4 AMR

AF:

0.364

Gnomad4 ASJ

AF:

0.270

Gnomad4 EAS

AF:

0.449

Gnomad4 SAS

AF:

0.357

Gnomad4 FIN

AF:

0.290

Gnomad4 NFE

AF:

0.248

Gnomad4 OTH

AF:

0.265

Alfa

AF:

0.184

Hom.:

100

ExAC

AF:

0.304

AC:

36885

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 07, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.81

DEOGEN2

Benign

0.0024

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

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.46

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.49

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

MetaRNN

Benign

0.0016

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

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.23

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

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.22

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

REVEL

Benign

0.10

Sift

Benign

0.18

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

Sift4G

Benign

0.49

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

Polyphen

0.0050, 0.048

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

Vest4

0.12

MPC

0.11

ClinPred

0.0013

GERP RS

2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.037

gMVP

0.13

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