3-123097025-A-G

Variant names:

• chr3-123097025-A-G
• rs3792361
• NM_006810.4:c.257+4583A>G

Variant summary

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

The NM_006810.4(PDIA5):​c.257+4583A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 152,190 control chromosomes in the GnomAD database, including 2,118 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 0.15 (2118 hom., cov: 32)
• Consequence: PDIA5 NM_006810.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.378
• Publications: 3 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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006810.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDIA5	NM_006810.4	MANE Select	c.257+4583A>G		intron	N/A	NP_006801.1
	PDIA5	NR_028444.2		n.397+4583A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDIA5	ENST00000316218.12	TSL:1 MANE Select	c.257+4583A>G		intron	N/A	ENSP00000323313.7
	PDIA5	ENST00000489923.5	TSL:1	n.257+4583A>G		intron	N/A	ENSP00000417520.1
	PDIA5	ENST00000484644.5	TSL:5	c.-32+4583A>G		intron	N/A	ENSP00000419946.1

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23182 AN: 152072 Hom.: 2116 Cov.: 32

Gnomad AFR AF: 0.0599

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.0966

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.137

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

GnomAD4 genome AF: 0.152 AC: 23191 AN: 152190 Hom.: 2118 Cov.: 32 AF XY: 0.151 AC XY: 11232 AN XY: 74388

African (AFR) AF: 0.0599 AC: 2488 AN: 41540

American (AMR) AF: 0.104 AC: 1589 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 439 AN: 3468

East Asian (EAS) AF: 0.0966 AC: 501 AN: 5184

South Asian (SAS) AF: 0.159 AC: 765 AN: 4820

European-Finnish (FIN) AF: 0.227 AC: 2402 AN: 10588

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.214 AC: 14557 AN: 67982

Other (OTH) AF: 0.134 AC: 284 AN: 2112

Alfa AF: 0.194 Hom.: 1937

Bravo AF: 0.139

Asia WGS AF: 0.109 AC: 380 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.6
DANN	Benign	0.84
PhyloP100		0.38
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3792361; hg19: chr3-122815872;