rs8040336

Variant names:

• chr15-43761419-C-A
• rs8040336
• NM_005313.5:c.365-5C>A

Your query was ambiguous. Multiple possible variants found:

• chr15-43761419-C-A
• chr15-43761419-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005313.5(PDIA3):​c.365-5C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PDIA3 NM_005313.5 splice_region, intron
• Scores: Splicing: ADA: 0.002504
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0260
• Publications: 22 publications found

Genes affected

PDIA3 (HGNC:4606): (protein disulfide isomerase family A member 3) This gene encodes a protein of the endoplasmic reticulum that interacts with lectin chaperones calreticulin and calnexin to modulate folding of newly synthesized glycoproteins. The protein was once thought to be a phospholipase; however, it has been demonstrated that the protein actually has protein disulfide isomerase activity. It is thought that complexes of lectins and this protein mediate protein folding by promoting formation of disulfide bonds in their glycoprotein substrates. This protein also functions as a molecular chaperone that prevents the formation of protein aggregates. [provided by RefSeq, Dec 2016]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDIA3	NM_005313.5	c.365-5C>A		splice_region_variant, intron_variant	Intron 3 of 12	ENST00000300289.10	NP_005304.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDIA3	ENST00000300289.10	c.365-5C>A		splice_region_variant, intron_variant	Intron 3 of 12	1	NM_005313.5	ENSP00000300289.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1353828 Hom.: 0 Cov.: 19 AF XY: 0.00 AC XY: 0 AN XY: 678320

African (AFR) AF: 0.00 AC: 0 AN: 30668

American (AMR) AF: 0.00 AC: 0 AN: 39692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24816

East Asian (EAS) AF: 0.00 AC: 0 AN: 39078

South Asian (SAS) AF: 0.00 AC: 0 AN: 80996

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53084

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5510

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1023404

Other (OTH) AF: 0.00 AC: 0 AN: 56580

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 41757

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	9.8
DANN	Benign	0.53
PhyloP100		-0.026

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0025
dbscSNV1_RF	Benign	0.054
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

Other links and lift over

dbSNP: rs8040336; hg19: chr15-44053617;