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. Variant got -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

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.925 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDIA5	NM_006810.4	c.342-120T>A		intron_variant	Intron 4 of 16	ENST00000316218.12	NP_006801.1
PDIA5	NR_028444.2	n.482-120T>A		intron_variant	Intron 4 of 15
PDIA5	XR_007095629.1	n.482-120T>A		intron_variant	Intron 4 of 13
PDIA5	XR_007095630.1	n.482-120T>A		intron_variant	Intron 4 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDIA5	ENST00000316218.12	c.342-120T>A		intron_variant	Intron 4 of 16	1	NM_006810.4	ENSP00000323313.7
PDIA5	ENST00000489923.5	n.342-120T>A		intron_variant	Intron 4 of 15	1		ENSP00000417520.1
PDIA5	ENST00000484644.5	c.54-120T>A		intron_variant	Intron 4 of 5	5		ENSP00000419946.1
PDIA5	ENST00000495004.1	n.361-120T>A		intron_variant	Intron 3 of 5	3

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

Gnomad4 AFR exome AF: 0.625

Gnomad4 AMR exome AF: 0.780

Gnomad4 ASJ exome AF: 0.831

Gnomad4 EAS exome AF: 0.763

Gnomad4 SAS exome AF: 0.782

Gnomad4 FIN exome AF: 0.952

Gnomad4 NFE exome AF: 0.879

Gnomad4 OTH exome AF: 0.844

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

Gnomad4 AFR AF: 0.679

Gnomad4 AMR AF: 0.842

Gnomad4 ASJ AF: 0.870

Gnomad4 EAS AF: 0.771

Gnomad4 SAS AF: 0.812

Gnomad4 FIN AF: 0.982

Gnomad4 NFE AF: 0.931

Gnomad4 OTH AF: 0.854

Alfa AF: 0.892 Hom.: 7019

Bravo AF: 0.827

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.0090
DANN	Benign	0.34

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

Publications

LitVar

Other links and lift over

dbSNP: rs2241962; hg19: chr3-122821478;