rs112946863

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_005313.5(PDIA3):c.56C>T(p.Ala19Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000544 in 1,611,426 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0031 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00027 ( 2 hom. )

Consequence

PDIA3
NM_005313.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.09

Publications

3 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006157458).

BP6

Variant 15-43746595-C-T is Benign according to our data. Variant chr15-43746595-C-T is described in ClinVar as Benign. ClinVar VariationId is 727554.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 479 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005313.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDIA3	NM_005313.5	MANE Select	c.56C>T	p.Ala19Val	missense	Exon 1 of 13	NP_005304.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PDIA3	ENST00000300289.10	TSL:1 MANE Select	c.56C>T	p.Ala19Val	missense	Exon 1 of 13	ENSP00000300289.5	P30101
PDIA3	ENST00000688851.1		c.56C>T	p.Ala19Val	missense	Exon 1 of 13	ENSP00000510205.1	A0A8I5KT88
PDIA3	ENST00000891522.1		c.56C>T	p.Ala19Val	missense	Exon 1 of 13	ENSP00000561581.1

Frequencies

GnomAD3 genomes

AF:

0.00314

AC:

478

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0113

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000955

GnomAD2 exomes

AF:

0.000726

AC:

174

AN:

239796

AF XY:

0.000485

show subpopulations

Gnomad AFR exome

AF:

0.0120

Gnomad AMR exome

AF:

0.000117

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000933

Gnomad OTH exome

AF:

0.000339

GnomAD4 exome

AF:

0.000273

AC:

398

AN:

1459062

Hom.:

Cov.:

AF XY:

0.000214

AC XY:

155

AN XY:

725894

show subpopulations

African (AFR)

AF:

0.0104

AC:

348

AN:

33458

American (AMR)

AF:

0.000358

AC:

AN:

44680

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26092

East Asian (EAS)

AF:

0.00

AC:

AN:

39676

South Asian (SAS)

AF:

0.00

AC:

AN:

86224

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51432

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5736

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111516

Other (OTH)

AF:

0.000531

AC:

AN:

60248

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

105

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00314

AC:

479

AN:

152364

Hom.:

Cov.:

AF XY:

0.00293

AC XY:

218

AN XY:

74506

show subpopulations

African (AFR)

AF:

0.0113

AC:

469

AN:

41592

American (AMR)

AF:

0.000457

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68032

Other (OTH)

AF:

0.000945

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

106

132

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.000364

Hom.:

Bravo

AF:

0.00345

ESP6500AA

AF:

0.00880

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000926

AC:

110

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.097

Eigen

Benign

-0.051

Eigen_PC

Benign

-0.084

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.61

MetaRNN

Benign

0.0062

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.3

PhyloP100

1.1

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

0.14

REVEL

Benign

0.15

Sift

Benign

0.32

Sift4G

Benign

0.68

Polyphen

0.98

Vest4

0.45

MVP

0.47

MPC

0.89

ClinPred

0.076

GERP RS

4.0

PromoterAI

-0.089

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.6

Varity_R

0.045

gMVP

0.64

Mutation Taster

=72/28

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over