rs6438779

Positions:

• chr3-123179882-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000469649.1(PDIA5):​c.232+18427T>C variant causes a intron, NMD transcript 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, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.55

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDIA5	ENST00000469649.1	c.232+18427T>C		intron_variant, NMD_transcript_variant		5		ENSP00000417199

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

Gnomad4 AFR AF: 0.951

Gnomad4 AMR AF: 0.814

Gnomad4 ASJ AF: 0.763

Gnomad4 EAS AF: 0.481

Gnomad4 SAS AF: 0.785

Gnomad4 FIN AF: 0.835

Gnomad4 NFE AF: 0.852

Gnomad4 OTH AF: 0.831

Alfa AF: 0.847 Hom.: 73168

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6438779; hg19: chr3-122898729;