rs11720822

Positions:

• chr3-123150194-C-T

Variant summary

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

The NM_006810.4(PDIA5):​c.1143-40C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.073 in 1,545,620 control chromosomes in the GnomAD database, including 5,335 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 0.066 (528 hom., cov: 32)
  • Exomes 𝑓: 0.074 (4807 hom.)
• Consequence: PDIA5 NM_006810.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.863

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDIA5	NM_006810.4	c.1143-40C>T		intron_variant		ENST00000316218.12
PDIA5	NR_028444.2	n.1127-40C>T		intron_variant, non_coding_transcript_variant
PDIA5	XR_007095629.1	n.1264-40C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDIA5	ENST00000316218.12	c.1143-40C>T		intron_variant		1	NM_006810.4	P1
PDIA5	ENST00000489923.5	c.*198-40C>T		intron_variant, NMD_transcript_variant		1
PDIA5	ENST00000467157.1	n.1248-40C>T		intron_variant, non_coding_transcript_variant		2
PDIA5	ENST00000485208.1	n.368-40C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0658 AC: 10004 AN: 152066 Hom.: 527 Cov.: 32

Gnomad AFR AF: 0.0173

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.0467

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0469

Gnomad FIN AF: 0.0895

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0759

Gnomad OTH AF: 0.0527

GnomAD3 exomes AF: 0.0862 AC: 19272 AN: 223514 Hom.: 1449 AF XY: 0.0814 AC XY: 9923 AN XY: 121874

Gnomad AFR exome AF: 0.0164

Gnomad AMR exome AF: 0.255

Gnomad ASJ exome AF: 0.0488

Gnomad EAS exome AF: 0.000289

Gnomad SAS exome AF: 0.0525

Gnomad FIN exome AF: 0.0839

Gnomad NFE exome AF: 0.0744

Gnomad OTH exome AF: 0.0747

GnomAD4 exome AF: 0.0737 AC: 102745 AN: 1393436 Hom.: 4807 Cov.: 25 AF XY: 0.0729 AC XY: 50608 AN XY: 694434

Gnomad4 AFR exome AF: 0.0118

Gnomad4 AMR exome AF: 0.242

Gnomad4 ASJ exome AF: 0.0514

Gnomad4 EAS exome AF: 0.000204

Gnomad4 SAS exome AF: 0.0520

Gnomad4 FIN exome AF: 0.0870

Gnomad4 NFE exome AF: 0.0740

Gnomad4 OTH exome AF: 0.0702

GnomAD4 genome AF: 0.0658 AC: 10008 AN: 152184 Hom.: 528 Cov.: 32 AF XY: 0.0671 AC XY: 4990 AN XY: 74392

Gnomad4 AFR AF: 0.0173

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.0467

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0471

Gnomad4 FIN AF: 0.0895

Gnomad4 NFE AF: 0.0759

Gnomad4 OTH AF: 0.0522

Alfa AF: 0.0747 Hom.: 168

Bravo AF: 0.0710

Asia WGS AF: 0.0280 AC: 98 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.91
DANN	Benign	0.72

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

Other links and lift over

dbSNP: rs11720822; hg19: chr3-122869041; COSMIC: COSV60248820; COSMIC: COSV60248820;