Variant 15-43761419-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005313.5(PDIA3):c.365-5C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 1,502,440 control chromosomes in the GnomAD database, including 206,733 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 16503 hom., cov: 31)

Exomes 𝑓: 0.52 ( 190230 hom. )

Consequence

PDIA3
NM_005313.5 splice_region, intron

Scores

Splicing: ADA: 0.00006908

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0260

Variant links:

Genes affected

PDIA3 (HGNC:4606): (protein disulfide isomerase family A member 3) This gene encodes a protein of the endoplasmic reticulum that interacts with lectin chaperones calreticulin and calnexin to modulate folding of newly synthesized glycoproteins. The protein was once thought to be a phospholipase; however, it has been demonstrated that the protein actually has protein disulfide isomerase activity. It is thought that complexes of lectins and this protein mediate protein folding by promoting formation of disulfide bonds in their glycoprotein substrates. This protein also functions as a molecular chaperone that prevents the formation of protein aggregates. [provided by RefSeq, Dec 2016]

PDIA3 links:

PDIA3 (HGNC:):

PDIA3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 15-43761419-C-T is Benign according to our data. Variant chr15-43761419-C-T is described in ClinVar as [Benign]. Clinvar id is 1250388.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDIA3	NM_005313.5 linkuse as main transcript	c.365-5C>T		splice_region_variant, intron_variant		ENST00000300289.10	NP_005304.3	P30101V9HVY3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDIA3	ENST00000300289.10 linkuse as main transcript	c.365-5C>T		splice_region_variant, intron_variant		1	NM_005313.5	ENSP00000300289.5		P30101

Frequencies

GnomAD3 genomes

AF:

0.422

AC:

64140

AN:

151828

Hom.:

16500

Cov.:

show subpopulations

Gnomad AFR

AF:

0.122

Gnomad AMI

AF:

0.523

Gnomad AMR

AF:

0.525

Gnomad ASJ

AF:

0.407

Gnomad EAS

AF:

0.431

Gnomad SAS

AF:

0.495

Gnomad FIN

AF:

0.680

Gnomad MID

AF:

0.345

Gnomad NFE

AF:

0.536

Gnomad OTH

AF:

0.437

GnomAD3 exomes

AF:

0.500

AC:

117875

AN:

235742

Hom.:

31278

AF XY:

0.506

AC XY:

64638

AN XY:

127742

show subpopulations

Gnomad AFR exome

AF:

0.117

Gnomad AMR exome

AF:

0.554

Gnomad ASJ exome

AF:

0.392

Gnomad EAS exome

AF:

0.402

Gnomad SAS exome

AF:

0.486

Gnomad FIN exome

AF:

0.672

Gnomad NFE exome

AF:

0.534

Gnomad OTH exome

AF:

0.518

GnomAD4 exome

AF:

0.524

AC:

707149

AN:

1350494

Hom.:

190230

Cov.:

AF XY:

0.522

AC XY:

353249

AN XY:

676734

show subpopulations

Gnomad4 AFR exome

AF:

0.103

Gnomad4 AMR exome

AF:

0.554

Gnomad4 ASJ exome

AF:

0.403

Gnomad4 EAS exome

AF:

0.460

Gnomad4 SAS exome

AF:

0.481

Gnomad4 FIN exome

AF:

0.665

Gnomad4 NFE exome

AF:

0.539

Gnomad4 OTH exome

AF:

0.492

GnomAD4 genome

AF:

0.422

AC:

64160

AN:

151946

Hom.:

16503

Cov.:

AF XY:

0.432

AC XY:

32042

AN XY:

74218

show subpopulations

Gnomad4 AFR

AF:

0.122

Gnomad4 AMR

AF:

0.525

Gnomad4 ASJ

AF:

0.407

Gnomad4 EAS

AF:

0.431

Gnomad4 SAS

AF:

0.496

Gnomad4 FIN

AF:

0.680

Gnomad4 NFE

AF:

0.536

Gnomad4 OTH

AF:

0.437

Alfa

AF:

0.502

Hom.:

31453

Bravo

AF:

0.396

Asia WGS

AF:

0.459

AC:

1594

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

PDIA3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

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

-0.79

CADD

Benign

8.8

DANN

Benign

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000069

dbscSNV1_RF

Benign

0.0

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over