rs702029

Positions:

• chr3-123129430-T-C
• chr3-123129430-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.774-1050T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.726 in 152,134 control chromosomes in the GnomAD database, including 40,725 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 0.73 (40725 hom., cov: 33)
• Consequence: PDIA5 NM_006810.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.312

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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDIA5	NM_006810.4	c.774-1050T>C		intron_variant		ENST00000316218.12
PDIA5	NR_028444.2	n.913+5087T>C		intron_variant, non_coding_transcript_variant
PDIA5	XR_007095629.1	n.914-1050T>C		intron_variant, non_coding_transcript_variant
PDIA5	XR_007095630.1	n.913+5087T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDIA5	ENST00000316218.12	c.774-1050T>C		intron_variant		1	NM_006810.4	P1
PDIA5	ENST00000489923.5	c.773+5087T>C		intron_variant, NMD_transcript_variant		1
PDIA5	ENST00000472319.5	n.164+5087T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.726 AC: 110294 AN: 152018 Hom.: 40695 Cov.: 33

Gnomad AFR AF: 0.612

Gnomad AMI AF: 0.828

Gnomad AMR AF: 0.741

Gnomad ASJ AF: 0.759

Gnomad EAS AF: 0.520

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.787

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.798

Gnomad OTH AF: 0.732

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

GnomAD4 genome AF: 0.726 AC: 110380 AN: 152134 Hom.: 40725 Cov.: 33 AF XY: 0.725 AC XY: 53897 AN XY: 74376

Gnomad4 AFR AF: 0.613

Gnomad4 AMR AF: 0.741

Gnomad4 ASJ AF: 0.759

Gnomad4 EAS AF: 0.520

Gnomad4 SAS AF: 0.665

Gnomad4 FIN AF: 0.787

Gnomad4 NFE AF: 0.798

Gnomad4 OTH AF: 0.732

Alfa AF: 0.767 Hom.: 5293

Bravo AF: 0.715

Asia WGS AF: 0.604 AC: 2105 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.0
DANN	Benign	0.41

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: rs702029; hg19: chr3-122848277; COSMIC: COSV60248011;