3-123155951-A-G

Variant names:

• chr3-123155951-A-G
• rs2667465
• NM_006810.4:c.1344+910A>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.1344+910A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 151,656 control chromosomes in the GnomAD database, including 25,505 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 0.57 (25505 hom., cov: 30)
• Consequence: PDIA5 NM_006810.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.504
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.73 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDIA5	NM_006810.4	MANE Select	c.1344+910A>G		intron	N/A	NP_006801.1	Q14554-1
	PDIA5	NR_028444.2		n.1328+910A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDIA5	ENST00000316218.12	TSL:1 MANE Select	c.1344+910A>G		intron	N/A	ENSP00000323313.7	Q14554-1
	PDIA5	ENST00000489923.5	TSL:1	n.*399+910A>G		intron	N/A	ENSP00000417520.1	Q14554-2
	PDIA5	ENST00000872610.1		c.1215+910A>G		intron	N/A	ENSP00000542669.1

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86525 AN: 151538 Hom.: 25454 Cov.: 30

Gnomad AFR AF: 0.737

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.539

Gnomad SAS AF: 0.545

Gnomad FIN AF: 0.541

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.566

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

GnomAD4 genome AF: 0.571 AC: 86635 AN: 151656 Hom.: 25505 Cov.: 30 AF XY: 0.571 AC XY: 42259 AN XY: 74050

African (AFR) AF: 0.737 AC: 30463 AN: 41338

American (AMR) AF: 0.481 AC: 7337 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.559 AC: 1937 AN: 3464

East Asian (EAS) AF: 0.540 AC: 2755 AN: 5100

South Asian (SAS) AF: 0.544 AC: 2605 AN: 4790

European-Finnish (FIN) AF: 0.541 AC: 5672 AN: 10490

Middle Eastern (MID) AF: 0.442 AC: 129 AN: 292

European-Non Finnish (NFE) AF: 0.501 AC: 34017 AN: 67914

Other (OTH) AF: 0.568 AC: 1197 AN: 2106

Alfa AF: 0.555 Hom.: 3100

Bravo AF: 0.573

Asia WGS AF: 0.597 AC: 2076 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.46
PhyloP100		-0.50
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2667465; hg19: chr3-122874798;