rs3792390

Positions:

• chr3-123141234-T-C
• chr3-123141234-T-G

Variant summary

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

The NM_006810.4(PDIA5):​c.911-4288T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 152,176 control chromosomes in the GnomAD database, including 2,937 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 0.18 (2937 hom., cov: 32)
• Consequence: PDIA5 NM_006810.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.574

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]

PDIA5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDIA5	NM_006810.4	c.911-4288T>C		intron_variant		ENST00000316218.12	NP_006801.1
PDIA5	NR_028444.2	n.914-4288T>C		intron_variant
PDIA5	XR_007095629.1	n.1051-4288T>C		intron_variant
PDIA5	XR_007095630.1	n.914-4288T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDIA5	ENST00000316218.12	c.911-4288T>C		intron_variant		1	NM_006810.4	ENSP00000323313.7
PDIA5	ENST00000489923.5	n.774-4288T>C		intron_variant		1		ENSP00000417520.1
PDIA5	ENST00000472319.5	n.165-4288T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27584 AN: 152058 Hom.: 2933 Cov.: 32

Gnomad AFR AF: 0.0754

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.181 AC: 27593 AN: 152176 Hom.: 2937 Cov.: 32 AF XY: 0.188 AC XY: 14001 AN XY: 74392

Gnomad4 AFR AF: 0.0754

Gnomad4 AMR AF: 0.224

Gnomad4 ASJ AF: 0.205

Gnomad4 EAS AF: 0.179

Gnomad4 SAS AF: 0.275

Gnomad4 FIN AF: 0.300

Gnomad4 NFE AF: 0.210

Gnomad4 OTH AF: 0.185

Alfa AF: 0.209 Hom.: 4599

Bravo AF: 0.171

Asia WGS AF: 0.249 AC: 863 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.9
DANN	Benign	0.88
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs3792390; hg19: chr3-122860081; COSMIC: COSV60248094; COSMIC: COSV60248094;