dbSNP rs7200543: PDXDC1:p.Leu735Leu (chr16-15036113-A-G) – 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.2205A>G(p.Leu735Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 1,613,730 control chromosomes in the GnomAD database, including 82,550 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.30 ( 7527 hom., cov: 32)

Exomes 𝑓: 0.31 ( 75023 hom. )

Consequence

PDXDC1
NM_015027.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.524

Publications

65 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:

Genome browser will be placed here

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=-0.82).

BP6

Variant 16-15036113-A-G is Benign according to our data. Variant chr16-15036113-A-G is described in ClinVar as Benign. ClinVar VariationId is 3059969.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.524 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDXDC1	NM_015027.4 link	c.2205A>G	p.Leu735Leu	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.2205A>G	p.Leu735Leu	synonymous_variant	Exon 23 of 23	1	NM_015027.4	ENSP00000379691.4		Q6P996-1

Frequencies

GnomAD3 genomes

AF:

0.304

AC:

46238

AN:

151960

Hom.:

7505

Cov.:

show subpopulations

Gnomad AFR

AF:

0.223

Gnomad AMI

AF:

0.245

Gnomad AMR

AF:

0.442

Gnomad ASJ

AF:

0.318

Gnomad EAS

AF:

0.385

Gnomad SAS

AF:

0.403

Gnomad FIN

AF:

0.339

Gnomad MID

AF:

0.253

Gnomad NFE

AF:

0.304

Gnomad OTH

AF:

0.318

GnomAD2 exomes

AF:

0.351

AC:

88253

AN:

251272

AF XY:

0.346

show subpopulations

Gnomad AFR exome

AF:

0.218

Gnomad AMR exome

AF:

0.544

Gnomad ASJ exome

AF:

0.323

Gnomad EAS exome

AF:

0.403

Gnomad FIN exome

AF:

0.335

Gnomad NFE exome

AF:

0.301

Gnomad OTH exome

AF:

0.335

GnomAD4 exome

AF:

0.315

AC:

459846

AN:

1461652

Hom.:

75023

Cov.:

AF XY:

0.316

AC XY:

229825

AN XY:

727150

show subpopulations

African (AFR)

AF:

0.224

AC:

7507

AN:

33480

American (AMR)

AF:

0.534

AC:

23881

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.320

AC:

8353

AN:

26132

East Asian (EAS)

AF:

0.422

AC:

16758

AN:

39700

South Asian (SAS)

AF:

0.381

AC:

32875

AN:

86254

European-Finnish (FIN)

AF:

0.325

AC:

17318

AN:

53362

Middle Eastern (MID)

AF:

0.277

AC:

1595

AN:

5768

European-Non Finnish (NFE)

AF:

0.299

AC:

332217

AN:

1111854

Other (OTH)

AF:

0.320

AC:

19342

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

18352

36704

55056

73408

91760

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11112

22224

33336

44448

55560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.305

AC:

46308

AN:

152078

Hom.:

7527

Cov.:

AF XY:

0.310

AC XY:

23073

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.223

AC:

9258

AN:

41492

American (AMR)

AF:

0.442

AC:

6748

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.318

AC:

1102

AN:

3468

East Asian (EAS)

AF:

0.386

AC:

1997

AN:

5172

South Asian (SAS)

AF:

0.404

AC:

1952

AN:

4826

European-Finnish (FIN)

AF:

0.339

AC:

3587

AN:

10576

Middle Eastern (MID)

AF:

0.262

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.304

AC:

20681

AN:

67960

Other (OTH)

AF:

0.324

AC:

683

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1639

3277

4916

6554

8193

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

468

936

1404

1872

2340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.308

Hom.:

32849

Bravo

AF:

0.311

Asia WGS

AF:

0.432

AC:

1502

AN:

3478

EpiCase

AF:

0.294

EpiControl

AF:

0.295

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PDXDC1-related disorder

Benign:1

Oct 17, 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

-0.82

CADD

Benign

3.7

(source)

DANN

Benign

0.69

PhyloP100

0.52

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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