Genetic Variant PDILT:c.681+29A>G (chr16-20374793-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_174924.2(PDILT):c.681+29A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.869 in 1,594,980 control chromosomes in the GnomAD database, including 612,705 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 0.80 ( 50374 hom., cov: 31)

Exomes 𝑓: 0.88 ( 562331 hom. )

Consequence

PDILT
NM_174924.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.63

Publications

12 publications found

Variant links:

Genes affected

PDILT (HGNC:27338): (protein disulfide isomerase like, testis expressed) 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 has an N-terminal ER-signal sequence, two thioredoxin (TRX) domains with non-classical Ser-Lys-Gln-Ser and Ser-Lys-Lys-Cys motifs, respectively, two TRX-like domains, and a C-terminal ER-retention sequence. The protein lacks oxidoreductase activity in vitro and probably functions as a chaperone. This gene's expression appears to be limited to the testis. [provided by RefSeq, Dec 2016]

PDILT links:

Genome browser will be placed here

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=-0.94).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.905 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDILT	NM_174924.2 link	c.681+29A>G		intron_variant	Intron 5 of 11	ENST00000302451.9	NP_777584.1	Q8N807

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDILT	ENST00000302451.9 link	c.681+29A>G		intron_variant	Intron 5 of 11	1	NM_174924.2	ENSP00000305465.4		Q8N807

Frequencies

GnomAD3 genomes

AF:

0.803

AC:

122068

AN:

152002

Hom.:

50359

Cov.:

show subpopulations

Gnomad AFR

AF:

0.687

Gnomad AMI

AF:

0.902

Gnomad AMR

AF:

0.745

Gnomad ASJ

AF:

0.873

Gnomad EAS

AF:

0.344

Gnomad SAS

AF:

0.774

Gnomad FIN

AF:

0.854

Gnomad MID

AF:

0.861

Gnomad NFE

AF:

0.911

Gnomad OTH

AF:

0.802

GnomAD2 exomes

AF:

0.795

AC:

189341

AN:

238130

AF XY:

0.809

show subpopulations

Gnomad AFR exome

AF:

0.680

Gnomad AMR exome

AF:

0.656

Gnomad ASJ exome

AF:

0.869

Gnomad EAS exome

AF:

0.327

Gnomad FIN exome

AF:

0.863

Gnomad NFE exome

AF:

0.907

Gnomad OTH exome

AF:

0.835

GnomAD4 exome

AF:

0.876

AC:

1263313

AN:

1442860

Hom.:

562331

Cov.:

AF XY:

0.875

AC XY:

626735

AN XY:

715958

show subpopulations

African (AFR)

AF:

0.687

AC:

22531

AN:

32778

American (AMR)

AF:

0.668

AC:

27951

AN:

41856

Ashkenazi Jewish (ASJ)

AF:

0.869

AC:

21807

AN:

25094

East Asian (EAS)

AF:

0.339

AC:

13389

AN:

39458

South Asian (SAS)

AF:

0.808

AC:

66775

AN:

82662

European-Finnish (FIN)

AF:

0.873

AC:

46270

AN:

52980

Middle Eastern (MID)

AF:

0.844

AC:

4789

AN:

5674

European-Non Finnish (NFE)

AF:

0.915

AC:

1009386

AN:

1102670

Other (OTH)

AF:

0.845

AC:

50415

AN:

59688

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

6610

13220

19830

26440

33050

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21286

42572

63858

85144

106430

<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:

0.803

AC:

122125

AN:

152120

Hom.:

50374

Cov.:

AF XY:

0.795

AC XY:

59127

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.686

AC:

28462

AN:

41476

American (AMR)

AF:

0.744

AC:

11381

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.873

AC:

3030

AN:

3470

East Asian (EAS)

AF:

0.344

AC:

1775

AN:

5162

South Asian (SAS)

AF:

0.775

AC:

3730

AN:

4816

European-Finnish (FIN)

AF:

0.854

AC:

9039

AN:

10584

Middle Eastern (MID)

AF:

0.857

AC:

252

AN:

294

European-Non Finnish (NFE)

AF:

0.911

AC:

61945

AN:

68010

Other (OTH)

AF:

0.801

AC:

1690

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1093

2185

3278

4370

5463

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

858

1716

2574

3432

4290

<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:

0.872

Hom.:

100889

Bravo

AF:

0.784

Asia WGS

AF:

0.548

AC:

1911

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.41

(source)

DANN

Benign

0.32

PhyloP100

-1.6

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