NM_005742.4:c.19+4714T>C

Variant names:

• chr2-10807964-A-G
• rs17456162
• NM_005742.4:c.19+4714T>C

Variant summary

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

The NM_005742.4(PDIA6):​c.19+4714T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,240 control chromosomes in the GnomAD database, including 1,993 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 0.14 (1993 hom., cov: 33)
• Consequence: PDIA6 NM_005742.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.121
• Publications: 4 publications found

Genes affected

PDIA6 (HGNC:30168): (protein disulfide isomerase family A member 6) 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, two catalytically active thioredoxin (TRX) domains, a TRX-like domain, and a C-terminal ER-retention sequence. This protein inhibits the aggregation of misfolded proteins and exhibits both isomerase and chaperone activity. Alternative splicing results in multiple transcript variants encoding different isoforms. [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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDIA6	NM_005742.4	c.19+4714T>C		intron_variant	Intron 1 of 12	ENST00000272227.8	NP_005733.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDIA6	ENST00000272227.8	c.19+4714T>C		intron_variant	Intron 1 of 12	1	NM_005742.4	ENSP00000272227.4

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21742 AN: 152122 Hom.: 1997 Cov.: 33

Gnomad AFR AF: 0.0431

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.0627

Gnomad SAS AF: 0.0767

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.162

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

GnomAD4 genome AF: 0.143 AC: 21740 AN: 152240 Hom.: 1993 Cov.: 33 AF XY: 0.139 AC XY: 10341 AN XY: 74418

African (AFR) AF: 0.0431 AC: 1793 AN: 41560

American (AMR) AF: 0.134 AC: 2051 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 782 AN: 3468

East Asian (EAS) AF: 0.0627 AC: 325 AN: 5184

South Asian (SAS) AF: 0.0760 AC: 367 AN: 4832

European-Finnish (FIN) AF: 0.170 AC: 1800 AN: 10594

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14102 AN: 67998

Other (OTH) AF: 0.163 AC: 344 AN: 2112

Alfa AF: 0.161 Hom.: 398

Bravo AF: 0.138

Asia WGS AF: 0.0770 AC: 270 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.9
DANN	Benign	0.60
PhyloP100		0.12
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: rs17456162; hg19: chr2-10948090;