Variant 15-43746595-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000300289.10(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. 12/20 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
ENST00000300289.10 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.09

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:31054): (CATSPER2 pseudogene 1) Catsper genes belong to a family of putative cation channels that are specific to spermatozoa and localize to the flagellum. This gene is part of a tandem repeat on chromosome 15q15; this copy of the gene is thought to be a pseudogene. [provided by RefSeq, Oct 2008]

CATSPER2P1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 727554.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 479 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDIA3	NM_005313.5 linkuse as main transcript	c.56C>T	p.Ala19Val	missense_variant	1/13	ENST00000300289.10	NP_005304.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDIA3	ENST00000300289.10 linkuse as main transcript	c.56C>T	p.Ala19Val	missense_variant	1/13	1	NM_005313.5	ENSP00000300289	P3

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

GnomAD3 exomes

AF:

0.000726

AC:

174

AN:

239796

Hom.:

AF XY:

0.000485

AC XY:

AN XY:

132078

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 SAS 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

Gnomad4 AFR exome

AF:

0.0104

Gnomad4 AMR exome

AF:

0.000358

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.000531

GnomAD4 genome

AF:

0.00314

AC:

479

AN:

152364

Hom.:

Cov.:

AF XY:

0.00293

AC XY:

218

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.0113

Gnomad4 AMR

AF:

0.000457

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000287

Hom.:

Bravo

AF:

0.00345

ESP6500AA

AF:

0.00880

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000926

AC:

110

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.44

CADD

Benign

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

MutationTaster

Benign

1.0

D;D

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

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.6

Varity_R

0.045

gMVP

0.64

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