15-43761689-A-G

Variant summary

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

The ENST00000300289.10(PDIA3):​c.472+158A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 151,962 control chromosomes in the GnomAD database, including 2,607 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2607 hom., cov: 31)

Consequence

PDIA3
ENST00000300289.10 intron

Scores

2

Clinical Significance

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

Conservation

PhyloP100: -0.546
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
Variant 15-43761689-A-G is Benign according to our data. Variant chr15-43761689-A-G is described in ClinVar as [Benign]. Clinvar id is 1283207.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PDIA3NM_005313.5 linkuse as main transcriptc.472+158A>G intron_variant ENST00000300289.10 NP_005304.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PDIA3ENST00000300289.10 linkuse as main transcriptc.472+158A>G intron_variant 1 NM_005313.5 ENSP00000300289 P3

Frequencies

GnomAD3 genomes
AF:
0.161
AC:
24513
AN:
151846
Hom.:
2599
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.290
Gnomad AMI
AF:
0.107
Gnomad AMR
AF:
0.178
Gnomad ASJ
AF:
0.176
Gnomad EAS
AF:
0.274
Gnomad SAS
AF:
0.141
Gnomad FIN
AF:
0.0406
Gnomad MID
AF:
0.168
Gnomad NFE
AF:
0.0918
Gnomad OTH
AF:
0.150
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.162
AC:
24563
AN:
151962
Hom.:
2607
Cov.:
31
AF XY:
0.160
AC XY:
11859
AN XY:
74308
show subpopulations
Gnomad4 AFR
AF:
0.290
Gnomad4 AMR
AF:
0.178
Gnomad4 ASJ
AF:
0.176
Gnomad4 EAS
AF:
0.274
Gnomad4 SAS
AF:
0.142
Gnomad4 FIN
AF:
0.0406
Gnomad4 NFE
AF:
0.0918
Gnomad4 OTH
AF:
0.154
Alfa
AF:
0.129
Hom.:
233
Bravo
AF:
0.181

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingGeneDxJun 19, 2021- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
2.7
DANN
Benign
0.44

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.

Other links and lift over

dbSNP: rs12101756; hg19: chr15-44053887; COSMIC: COSV55857959; COSMIC: COSV55857959; API