Genetic Variant PDXDC1:c.22-8745C>T (chr16-14989008-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_015027.4(PDXDC1):c.22-8745C>T variant causes a intron change. The variant allele was found at a frequency of 0.264 in 1,549,084 control chromosomes in the GnomAD database, including 21,341 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.26 ( 2156 hom., cov: 52)

Exomes 𝑓: 0.26 ( 19185 hom. )

Consequence

PDXDC1
NM_015027.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.10

Publications

15 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:

ENSG00000261819 (HGNC:):

ENSG00000261819 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BS2

High Homozygotes in GnomAd4 at 2156 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDXDC1	NM_015027.4 link	c.22-8745C>T		intron_variant	Intron 1 of 22	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.22-8745C>T		intron_variant	Intron 1 of 22	1	NM_015027.4	ENSP00000379691.4		Q6P996-1

Frequencies

GnomAD3 genomes

AF:

0.256

AC:

37583

AN:

147006

Hom.:

2141

Cov.:

show subpopulations

Gnomad AFR

AF:

0.178

Gnomad AMI

AF:

0.213

Gnomad AMR

AF:

0.369

Gnomad ASJ

AF:

0.285

Gnomad EAS

AF:

0.451

Gnomad SAS

AF:

0.356

Gnomad FIN

AF:

0.291

Gnomad MID

AF:

0.176

Gnomad NFE

AF:

0.249

Gnomad OTH

AF:

0.264

GnomAD4 exome

AF:

0.265

AC:

370959

AN:

1401964

Hom.:

19185

Cov.:

AF XY:

0.267

AC XY:

186248

AN XY:

698510

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.180

AC:

5921

AN:

32816

American (AMR)

AF:

0.464

AC:

20364

AN:

43914

Ashkenazi Jewish (ASJ)

AF:

0.290

AC:

7396

AN:

25506

East Asian (EAS)

AF:

0.510

AC:

20137

AN:

39520

South Asian (SAS)

AF:

0.338

AC:

28677

AN:

84760

European-Finnish (FIN)

AF:

0.279

AC:

14530

AN:

52024

Middle Eastern (MID)

AF:

0.225

AC:

1266

AN:

5618

European-Non Finnish (NFE)

AF:

0.242

AC:

256721

AN:

1059396

Other (OTH)

AF:

0.273

AC:

15947

AN:

58410

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.369

Heterozygous variant carriers

16873

33747

50620

67494

84367

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9698

19396

29094

38792

48490

<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:

0.256

AC:

37639

AN:

147120

Hom.:

2156

Cov.:

AF XY:

0.262

AC XY:

18851

AN XY:

71884

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.179

AC:

7241

AN:

40530

American (AMR)

AF:

0.369

AC:

5432

AN:

14720

Ashkenazi Jewish (ASJ)

AF:

0.285

AC:

968

AN:

3398

East Asian (EAS)

AF:

0.451

AC:

2302

AN:

5100

South Asian (SAS)

AF:

0.357

AC:

1672

AN:

4684

European-Finnish (FIN)

AF:

0.291

AC:

2981

AN:

10240

Middle Eastern (MID)

AF:

0.180

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.249

AC:

16257

AN:

65260

Other (OTH)

AF:

0.271

AC:

545

AN:

2014

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.390

Heterozygous variant carriers

1471

2942

4413

5884

7355

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

430

860

1290

1720

2150

<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:

0.259

Hom.:

168

Asia WGS

AF:

0.423

AC:

1469

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.93

PhyloP100

5.1

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over