chr3-123179882-T-C

Variant names:

• chr3-123179882-T-C
• rs6438779
• ENST00000469649.1:n.231+18427T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000469649.1(PDIA5):​n.231+18427T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.857 in 152,214 control chromosomes in the GnomAD database, including 56,469 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.86 (56469 hom., cov: 32)
• Consequence: PDIA5 ENST00000469649.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.55
• Publications: 1 publications found

Genes affected

PDIA5 (HGNC:24811): (protein disulfide isomerase family A member 5) This gene encodes a member of the disulfide isomerase (PDI) family of endoplasmic reticulum (ER) proteins that catalyze protein folding and thiol-disulfide interchange reactions. The encoded protein has an N-terminal ER-signal sequence, three catalytically active thioredoxin (TRX) domains, a TRX-like domain, and a C-terminal ER-retention sequence. The N-terminal TRX-like domain is the primary binding site for the major ER chaperone calreticulin and possibly other proteins and substrates as well. Alternative splicing results in multiple protein- and non-protein-coding transcript variants. [provided by RefSeq, Dec 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.943 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDIA5	ENST00000469649.1	n.231+18427T>C		intron_variant	Intron 3 of 5	5		ENSP00000417199.1

Frequencies

GnomAD3 genomes AF: 0.857 AC: 130348 AN: 152096 Hom.: 56416 Cov.: 32

Gnomad AFR AF: 0.951

Gnomad AMI AF: 0.880

Gnomad AMR AF: 0.815

Gnomad ASJ AF: 0.763

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.786

Gnomad FIN AF: 0.835

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.852

Gnomad OTH AF: 0.833

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.857 AC: 130455 AN: 152214 Hom.: 56469 Cov.: 32 AF XY: 0.851 AC XY: 63315 AN XY: 74416

African (AFR) AF: 0.951 AC: 39520 AN: 41566

American (AMR) AF: 0.814 AC: 12446 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.763 AC: 2646 AN: 3470

East Asian (EAS) AF: 0.481 AC: 2488 AN: 5168

South Asian (SAS) AF: 0.785 AC: 3784 AN: 4822

European-Finnish (FIN) AF: 0.835 AC: 8823 AN: 10572

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.852 AC: 57963 AN: 68008

Other (OTH) AF: 0.831 AC: 1755 AN: 2112

Alfa AF: 0.848 Hom.: 101635

Bravo AF: 0.857

Asia WGS AF: 0.687 AC: 2385 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.10
DANN	Benign	0.62
PhyloP100		-3.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6438779; hg19: chr3-122898729;