rs4677994

chr3-123095206-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006810.4(PDIA5):c.257+2764C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0688 in 152,182 control chromosomes in the GnomAD database, including 507 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 0.069 (507 hom., cov: 32)
• Consequence: PDIA5 NM_006810.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0947 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDIA5	NM_006810.4	c.257+2764C>T		intron_variant		ENST00000316218.12
PDIA5	NR_028444.2	n.397+2764C>T		intron_variant, non_coding_transcript_variant
PDIA5	XR_007095629.1	n.397+2764C>T		intron_variant, non_coding_transcript_variant
PDIA5	XR_007095630.1	n.397+2764C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDIA5	ENST00000316218.12	c.257+2764C>T		intron_variant		1	NM_006810.4	P1
PDIA5	ENST00000489923.5	c.257+2764C>T		intron_variant, NMD_transcript_variant		1
PDIA5	ENST00000484644.5	c.-32+2764C>T		intron_variant		5
PDIA5	ENST00000495004.1	n.276+2764C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0689 AC: 10476 AN: 152064 Hom.: 508 Cov.: 32

Gnomad AFR AF: 0.0165

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.0790

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0990

Gnomad FIN AF: 0.0746

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.0967

Gnomad OTH AF: 0.0940

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

GnomAD4 genome AF: 0.0688 AC: 10475 AN: 152182 Hom.: 507 Cov.: 32 AF XY: 0.0695 AC XY: 5172 AN XY: 74392

Gnomad4 AFR AF: 0.0165

Gnomad4 AMR AF: 0.0789

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.0995

Gnomad4 FIN AF: 0.0746

Gnomad4 NFE AF: 0.0967

Gnomad4 OTH AF: 0.0920

Alfa AF: 0.0916 Hom.: 341

Bravo AF: 0.0646

Asia WGS AF: 0.0400 AC: 139 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	2.6
Dann	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4677994; hg19: chr3-122814053;