Genetic Variant PDIA3:p.Ala54Ala (chr15-43746701-C-T) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_005313.5(PDIA3):c.162C>T(p.Ala54Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.695 in 1,612,294 control chromosomes in the GnomAD database, including 398,635 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.60 ( 30219 hom., cov: 33)

Exomes 𝑓: 0.71 ( 368416 hom. )

Consequence

PDIA3
NM_005313.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.124

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:

CATSPER2P1 (HGNC:):

CATSPER2P1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 15-43746701-C-T is Benign according to our data. Variant chr15-43746701-C-T is described in ClinVar as [Benign]. Clinvar id is 1262760.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.124 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDIA3	NM_005313.5 link	c.162C>T	p.Ala54Ala	synonymous_variant	Exon 1 of 13	ENST00000300289.10	NP_005304.3	P30101V9HVY3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDIA3	ENST00000300289.10 link	c.162C>T	p.Ala54Ala	synonymous_variant	Exon 1 of 13	1	NM_005313.5	ENSP00000300289.5		P30101

Frequencies

GnomAD3 genomes

AF:

0.597

AC:

90834

AN:

152056

Hom.:

30215

Cov.:

show subpopulations

Gnomad AFR

AF:

0.284

Gnomad AMI

AF:

0.777

Gnomad AMR

AF:

0.659

Gnomad ASJ

AF:

0.631

Gnomad EAS

AF:

0.677

Gnomad SAS

AF:

0.637

Gnomad FIN

AF:

0.817

Gnomad MID

AF:

0.563

Gnomad NFE

AF:

0.726

Gnomad OTH

AF:

0.624

GnomAD3 exomes

AF:

0.680

AC:

166959

AN:

245642

Hom.:

58433

AF XY:

0.684

AC XY:

91807

AN XY:

134254

show subpopulations

Gnomad AFR exome

AF:

0.279

Gnomad AMR exome

AF:

0.695

Gnomad ASJ exome

AF:

0.620

Gnomad EAS exome

AF:

0.673

Gnomad SAS exome

AF:

0.631

Gnomad FIN exome

AF:

0.816

Gnomad NFE exome

AF:

0.722

Gnomad OTH exome

AF:

0.692

GnomAD4 exome

AF:

0.706

AC:

1030288

AN:

1460120

Hom.:

368416

Cov.:

AF XY:

0.704

AC XY:

511510

AN XY:

726412

show subpopulations

Gnomad4 AFR exome

AF:

0.268

Gnomad4 AMR exome

AF:

0.695

Gnomad4 ASJ exome

AF:

0.621

Gnomad4 EAS exome

AF:

0.677

Gnomad4 SAS exome

AF:

0.629

Gnomad4 FIN exome

AF:

0.816

Gnomad4 NFE exome

AF:

0.725

Gnomad4 OTH exome

AF:

0.681

GnomAD4 genome

AF:

0.597

AC:

90849

AN:

152174

Hom.:

30219

Cov.:

AF XY:

0.603

AC XY:

44873

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.284

Gnomad4 AMR

AF:

0.659

Gnomad4 ASJ

AF:

0.631

Gnomad4 EAS

AF:

0.678

Gnomad4 SAS

AF:

0.636

Gnomad4 FIN

AF:

0.817

Gnomad4 NFE

AF:

0.726

Gnomad4 OTH

AF:

0.622

Alfa

AF:

0.663

Hom.:

21418

Bravo

AF:

0.571

Asia WGS

AF:

0.637

AC:

2211

AN:

3478

EpiCase

AF:

0.713

EpiControl

AF:

0.710

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 09, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.83

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over