Genetic Variant PDIA5:c.1143-40C>T (chr3-123150194-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006810.4(PDIA5):c.1143-40C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.073 in 1,545,620 control chromosomes in the GnomAD database, including 5,335 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 0.066 ( 528 hom., cov: 32)

Exomes 𝑓: 0.074 ( 4807 hom. )

Consequence

PDIA5
NM_006810.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.863

Publications

11 publications found

Variant links:

Genes affected

PDIA5 (HGNC:24811): (protein disulfide isomerase family A member 5) This gene encodes a member of the disulfide isomerase (PDI) family of endoplasmic reticulum (ER) proteins that catalyze protein folding and thiol-disulfide interchange reactions. The encoded protein has an N-terminal ER-signal sequence, three catalytically active thioredoxin (TRX) domains, a TRX-like domain, and a C-terminal ER-retention sequence. The N-terminal TRX-like domain is the primary binding site for the major ER chaperone calreticulin and possibly other proteins and substrates as well. Alternative splicing results in multiple protein- and non-protein-coding transcript variants. [provided by RefSeq, Dec 2016]

PDIA5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PDIA5	NM_006810.4 link	c.1143-40C>T	intron_variant	Intron 13 of 16	ENST00000316218.12	NP_006801.1	Q14554-1
PDIA5	NR_028444.2 link	n.1127-40C>T	intron_variant	Intron 12 of 15
PDIA5	XR_007095629.1 link	n.1264-40C>T	intron_variant	Intron 13 of 13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDIA5	ENST00000316218.12 link	c.1143-40C>T		intron_variant	Intron 13 of 16	1	NM_006810.4	ENSP00000323313.7		Q14554-1

Frequencies

GnomAD3 genomes

AF:

0.0658

AC:

10004

AN:

152066

Hom.:

527

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0173

Gnomad AMI

AF:

0.0625

Gnomad AMR

AF:

0.170

Gnomad ASJ

AF:

0.0467

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.0469

Gnomad FIN

AF:

0.0895

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0759

Gnomad OTH

AF:

0.0527

GnomAD2 exomes

AF:

0.0862

AC:

19272

AN:

223514

AF XY:

0.0814

show subpopulations

Gnomad AFR exome

AF:

0.0164

Gnomad AMR exome

AF:

0.255

Gnomad ASJ exome

AF:

0.0488

Gnomad EAS exome

AF:

0.000289

Gnomad FIN exome

AF:

0.0839

Gnomad NFE exome

AF:

0.0744

Gnomad OTH exome

AF:

0.0747

GnomAD4 exome

AF:

0.0737

AC:

102745

AN:

1393436

Hom.:

4807

Cov.:

AF XY:

0.0729

AC XY:

50608

AN XY:

694434

show subpopulations

African (AFR)

AF:

0.0118

AC:

374

AN:

31802

American (AMR)

AF:

0.242

AC:

9550

AN:

39410

Ashkenazi Jewish (ASJ)

AF:

0.0514

AC:

1241

AN:

24154

East Asian (EAS)

AF:

0.000204

AC:

AN:

39208

South Asian (SAS)

AF:

0.0520

AC:

4238

AN:

81514

European-Finnish (FIN)

AF:

0.0870

AC:

4434

AN:

50994

Middle Eastern (MID)

AF:

0.0356

AC:

181

AN:

5090

European-Non Finnish (NFE)

AF:

0.0740

AC:

78664

AN:

1063470

Other (OTH)

AF:

0.0702

AC:

4055

AN:

57794

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

Heterozygous variant carriers

3510

7019

10529

14038

17548

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2942

5884

8826

11768

14710

<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:

0.0658

AC:

10008

AN:

152184

Hom.:

528

Cov.:

AF XY:

0.0671

AC XY:

4990

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.0173

AC:

717

AN:

41524

American (AMR)

AF:

0.170

AC:

2604

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0467

AC:

162

AN:

3470

East Asian (EAS)

AF:

0.00116

AC:

AN:

5188

South Asian (SAS)

AF:

0.0471

AC:

227

AN:

4818

European-Finnish (FIN)

AF:

0.0895

AC:

949

AN:

10602

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0759

AC:

5161

AN:

67986

Other (OTH)

AF:

0.0522

AC:

110

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

465

929

1394

1858

2323

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

216

324

432

540

<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:

0.0670

Hom.:

399

Bravo

AF:

0.0710

Asia WGS

AF:

0.0280

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.91

(source)

DANN

Benign

0.72

PhyloP100

-0.86

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