NM_006810.4:c.1143-40C>T

Variant names:

• chr3-123150194-C-T
• rs11720822
• NM_006810.4:c.1143-40C>T

Variant summary

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

The NM_006810.4(PDIA5):​c.1143-40C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.073 in 1,545,620 control chromosomes in the GnomAD database, including 5,335 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 0.066 (528 hom., cov: 32)
  • Exomes 𝑓: 0.074 (4807 hom.)
• Consequence: PDIA5 NM_006810.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.863
• Publications: 11 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDIA5	NM_006810.4	c.1143-40C>T		intron_variant	Intron 13 of 16	ENST00000316218.12	NP_006801.1
PDIA5	NR_028444.2	n.1127-40C>T		intron_variant	Intron 12 of 15
PDIA5	XR_007095629.1	n.1264-40C>T		intron_variant	Intron 13 of 13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDIA5	ENST00000316218.12	c.1143-40C>T		intron_variant	Intron 13 of 16	1	NM_006810.4	ENSP00000323313.7

Frequencies

GnomAD3 genomes AF: 0.0658 AC: 10004 AN: 152066 Hom.: 527 Cov.: 32

Gnomad AFR AF: 0.0173

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.0467

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0469

Gnomad FIN AF: 0.0895

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0759

Gnomad OTH AF: 0.0527

GnomAD2 exomes AF: 0.0862 AC: 19272 AN: 223514 AF XY: 0.0814

Gnomad AFR exome AF: 0.0164

Gnomad AMR exome AF: 0.255

Gnomad ASJ exome AF: 0.0488

Gnomad EAS exome AF: 0.000289

Gnomad FIN exome AF: 0.0839

Gnomad NFE exome AF: 0.0744

Gnomad OTH exome AF: 0.0747

GnomAD4 exome AF: 0.0737 AC: 102745 AN: 1393436 Hom.: 4807 Cov.: 25 AF XY: 0.0729 AC XY: 50608 AN XY: 694434

African (AFR) AF: 0.0118 AC: 374 AN: 31802

American (AMR) AF: 0.242 AC: 9550 AN: 39410

Ashkenazi Jewish (ASJ) AF: 0.0514 AC: 1241 AN: 24154

East Asian (EAS) AF: 0.000204 AC: 8 AN: 39208

South Asian (SAS) AF: 0.0520 AC: 4238 AN: 81514

European-Finnish (FIN) AF: 0.0870 AC: 4434 AN: 50994

Middle Eastern (MID) AF: 0.0356 AC: 181 AN: 5090

European-Non Finnish (NFE) AF: 0.0740 AC: 78664 AN: 1063470

Other (OTH) AF: 0.0702 AC: 4055 AN: 57794

GnomAD4 genome AF: 0.0658 AC: 10008 AN: 152184 Hom.: 528 Cov.: 32 AF XY: 0.0671 AC XY: 4990 AN XY: 74392

African (AFR) AF: 0.0173 AC: 717 AN: 41524

American (AMR) AF: 0.170 AC: 2604 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0467 AC: 162 AN: 3470

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5188

South Asian (SAS) AF: 0.0471 AC: 227 AN: 4818

European-Finnish (FIN) AF: 0.0895 AC: 949 AN: 10602

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0759 AC: 5161 AN: 67986

Other (OTH) AF: 0.0522 AC: 110 AN: 2108

Alfa AF: 0.0670 Hom.: 399

Bravo AF: 0.0710

Asia WGS AF: 0.0280 AC: 98 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.91
DANN	Benign	0.72
PhyloP100		-0.86
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: rs11720822; hg19: chr3-122869041; COSMIC: COSV60248820; COSMIC: COSV60248820;