Genetic Variant PDXDC1:p.His725His (chr16-15036083-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_015027.4(PDXDC1):c.2175C>T(p.His725His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 1,613,794 control chromosomes in the GnomAD database, including 115,870 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.28 ( 7872 hom., cov: 32)

Exomes 𝑓: 0.37 ( 107998 hom. )

Consequence

PDXDC1
NM_015027.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.0700

Publications

105 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 16-15036083-C-T is Benign according to our data. Variant chr16-15036083-C-T is described in ClinVar as [Benign]. Clinvar id is 3060524.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.07 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDXDC1	NM_015027.4 link	c.2175C>T	p.His725His	synonymous_variant	Exon 23 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.2175C>T	p.His725His	synonymous_variant	Exon 23 of 23	1	NM_015027.4	ENSP00000379691.4		Q6P996-1

Frequencies

GnomAD3 genomes

AF:

0.282

AC:

42853

AN:

152004

Hom.:

7874

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0753

Gnomad AMI

AF:

0.552

Gnomad AMR

AF:

0.255

Gnomad ASJ

AF:

0.391

Gnomad EAS

AF:

0.00347

Gnomad SAS

AF:

0.250

Gnomad FIN

AF:

0.400

Gnomad MID

AF:

0.418

Gnomad NFE

AF:

0.408

Gnomad OTH

AF:

0.311

GnomAD2 exomes

AF:

0.307

AC:

77081

AN:

251280

AF XY:

0.320

show subpopulations

Gnomad AFR exome

AF:

0.0684

Gnomad AMR exome

AF:

0.183

Gnomad ASJ exome

AF:

0.386

Gnomad EAS exome

AF:

0.00228

Gnomad FIN exome

AF:

0.394

Gnomad NFE exome

AF:

0.414

Gnomad OTH exome

AF:

0.358

GnomAD4 exome

AF:

0.371

AC:

542601

AN:

1461672

Hom.:

107998

Cov.:

AF XY:

0.370

AC XY:

269110

AN XY:

727148

show subpopulations

African (AFR)

AF:

0.0658

AC:

2202

AN:

33478

American (AMR)

AF:

0.191

AC:

8554

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.381

AC:

9966

AN:

26134

East Asian (EAS)

AF:

0.00209

AC:

AN:

39700

South Asian (SAS)

AF:

0.265

AC:

22856

AN:

86258

European-Finnish (FIN)

AF:

0.404

AC:

21559

AN:

53354

Middle Eastern (MID)

AF:

0.421

AC:

2431

AN:

5768

European-Non Finnish (NFE)

AF:

0.408

AC:

453740

AN:

1111878

Other (OTH)

AF:

0.351

AC:

21210

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

19856

39711

59567

79422

99278

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.282

AC:

42838

AN:

152122

Hom.:

7872

Cov.:

AF XY:

0.278

AC XY:

20699

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.0750

AC:

3117

AN:

41536

American (AMR)

AF:

0.254

AC:

3882

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.391

AC:

1355

AN:

3468

East Asian (EAS)

AF:

0.00348

AC:

AN:

5178

South Asian (SAS)

AF:

0.250

AC:

1208

AN:

4828

European-Finnish (FIN)

AF:

0.400

AC:

4233

AN:

10570

Middle Eastern (MID)

AF:

0.408

AC:

120

AN:

294

European-Non Finnish (NFE)

AF:

0.408

AC:

27753

AN:

67950

Other (OTH)

AF:

0.308

AC:

650

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1395

2790

4186

5581

6976

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.359

Hom.:

37148

Bravo

AF:

0.260

Asia WGS

AF:

0.108

AC:

380

AN:

3478

EpiCase

AF:

0.413

EpiControl

AF:

0.426

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PDXDC1-related disorder

Benign:1

Oct 16, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

8.6

(source)

DANN

Benign

0.80

PhyloP100

-0.070

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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chr16-15036083-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over