Variant 3-123150194-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 made for transcript

Verdict is Benign. Variant got -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	MANE
PDIA5	NM_006810.4 linkuse as main transcript	c.1143-40C>T	intron_variant	ENST00000316218.12
PDIA5	NR_028444.2 linkuse as main transcript	n.1127-40C>T	intron_variant, non_coding_transcript_variant
PDIA5	XR_007095629.1 linkuse as main transcript	n.1264-40C>T	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
PDIA5	ENST00000316218.12 linkuse as main transcript	c.1143-40C>T	intron_variant	1	NM_006810.4	P1	Q14554-1
PDIA5	ENST00000489923.5 linkuse as main transcript	c.*198-40C>T	intron_variant, NMD_transcript_variant	1			Q14554-2
PDIA5	ENST00000467157.1 linkuse as main transcript	n.1248-40C>T	intron_variant, non_coding_transcript_variant	2
PDIA5	ENST00000485208.1 linkuse as main transcript	n.368-40C>T	intron_variant, non_coding_transcript_variant	5

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

GnomAD3 exomes

AF:

0.0862

AC:

19272

AN:

223514

Hom.:

1449

AF XY:

0.0814

AC XY:

9923

AN XY:

121874

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 SAS exome

AF:

0.0525

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

Gnomad4 AFR exome

AF:

0.0118

Gnomad4 AMR exome

AF:

0.242

Gnomad4 ASJ exome

AF:

0.0514

Gnomad4 EAS exome

AF:

0.000204

Gnomad4 SAS exome

AF:

0.0520

Gnomad4 FIN exome

AF:

0.0870

Gnomad4 NFE exome

AF:

0.0740

Gnomad4 OTH exome

AF:

0.0702

GnomAD4 genome

AF:

0.0658

AC:

10008

AN:

152184

Hom.:

528

Cov.:

AF XY:

0.0671

AC XY:

4990

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.0173

Gnomad4 AMR

AF:

0.170

Gnomad4 ASJ

AF:

0.0467

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.0471

Gnomad4 FIN

AF:

0.0895

Gnomad4 NFE

AF:

0.0759

Gnomad4 OTH

AF:

0.0522

Alfa

AF:

0.0747

Hom.:

168

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

DANN

Benign

0.72

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over