rs2241962

Variant names:

• chr3-123102631-T-A
• rs2241962
• NM_006810.4:c.342-120T>A

Your query was ambiguous. Multiple possible variants found:

• chr3-123102631-T-A
• chr3-123102631-T-C
• chr3-123102631-T-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.342-120T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.854 in 817,868 control chromosomes in the GnomAD database, including 298,655 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 0.85 (55156 hom., cov: 32)
  • Exomes 𝑓: 0.86 (243499 hom.)
• Consequence: PDIA5 NM_006810.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49
• Publications: 8 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.925 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.342-120T>A		intron	N/A	NP_006801.1
	PDIA5	NR_028444.2		n.482-120T>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDIA5	ENST00000316218.12	TSL:1 MANE Select	c.342-120T>A		intron	N/A	ENSP00000323313.7
	PDIA5	ENST00000489923.5	TSL:1	n.342-120T>A		intron	N/A	ENSP00000417520.1
	PDIA5	ENST00000484644.5	TSL:5	c.54-120T>A		intron	N/A	ENSP00000419946.1

Frequencies

GnomAD3 genomes AF: 0.846 AC: 128164 AN: 151548 Hom.: 55135 Cov.: 32

Gnomad AFR AF: 0.679

Gnomad AMI AF: 0.970

Gnomad AMR AF: 0.843

Gnomad ASJ AF: 0.870

Gnomad EAS AF: 0.771

Gnomad SAS AF: 0.811

Gnomad FIN AF: 0.982

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.931

Gnomad OTH AF: 0.852

GnomAD4 exome AF: 0.856 AC: 570452 AN: 666202 Hom.: 243499 Cov.: 10 AF XY: 0.854 AC XY: 294247 AN XY: 344556

African (AFR) AF: 0.625 AC: 11271 AN: 18040

American (AMR) AF: 0.780 AC: 19580 AN: 25116

Ashkenazi Jewish (ASJ) AF: 0.831 AC: 14618 AN: 17582

East Asian (EAS) AF: 0.763 AC: 23661 AN: 31024

South Asian (SAS) AF: 0.782 AC: 42918 AN: 54860

European-Finnish (FIN) AF: 0.952 AC: 40444 AN: 42492

Middle Eastern (MID) AF: 0.864 AC: 3044 AN: 3524

European-Non Finnish (NFE) AF: 0.879 AC: 387478 AN: 441054

Other (OTH) AF: 0.844 AC: 27438 AN: 32510

GnomAD4 genome AF: 0.846 AC: 128236 AN: 151666 Hom.: 55156 Cov.: 32 AF XY: 0.848 AC XY: 62838 AN XY: 74094

African (AFR) AF: 0.679 AC: 28092 AN: 41360

American (AMR) AF: 0.842 AC: 12838 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.870 AC: 3013 AN: 3462

East Asian (EAS) AF: 0.771 AC: 3980 AN: 5160

South Asian (SAS) AF: 0.812 AC: 3893 AN: 4796

European-Finnish (FIN) AF: 0.982 AC: 10294 AN: 10486

Middle Eastern (MID) AF: 0.901 AC: 265 AN: 294

European-Non Finnish (NFE) AF: 0.931 AC: 63183 AN: 67856

Other (OTH) AF: 0.854 AC: 1793 AN: 2100

Alfa AF: 0.892 Hom.: 7019

Bravo AF: 0.827

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.0090
DANN	Benign	0.34
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2241962; hg19: chr3-122821478; COSMIC: COSV107336562;