rs747857317

Variant names:

• chr15-43765434-CTTTTT-C
• rs747857317
• NM_005313.5:c.603-8_603-4delTTTTT

Your query was ambiguous. Multiple possible variants found:

• chr15-43765434-CTTTTT-C
• chr15-43765434-CTTTTT-CTT
• chr15-43765434-CTTTTT-CTTT
• chr15-43765434-CTTTTT-CTTTT
• chr15-43765434-CTTTTT-CTTTTTT
• chr15-43765434-CTTTTT-CTTTTTTT
• chr15-43765434-CTTTTT-CTTTTTTTT
• chr15-43765434-CTTTTT-CTTTTTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005313.5(PDIA3):​c.603-8_603-4delTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000957 in 1,044,410 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 9.6e-7 (0 hom.)
• Consequence: PDIA3 NM_005313.5 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.41
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005313.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDIA3	NM_005313.5	MANE Select	c.603-8_603-4delTTTTT		splice_region intron	N/A	NP_005304.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDIA3	ENST00000300289.10	TSL:1 MANE Select	c.603-8_603-4delTTTTT		splice_region intron	N/A	ENSP00000300289.5	P30101
	PDIA3	ENST00000688851.1		c.603-8_603-4delTTTTT		splice_region intron	N/A	ENSP00000510205.1	A0A8I5KT88
	PDIA3	ENST00000891522.1		c.585-8_585-4delTTTTT		splice_region intron	N/A	ENSP00000561581.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 9.57e-7 AC: 1 AN: 1044410 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 531224

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 23824

American (AMR) AF: 0.00 AC: 0 AN: 33958

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20748

East Asian (EAS) AF: 0.00 AC: 0 AN: 33886

South Asian (SAS) AF: 0.00 AC: 0 AN: 68502

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45486

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4546

European-Non Finnish (NFE) AF: 0.00000130 AC: 1 AN: 768566

Other (OTH) AF: 0.00 AC: 0 AN: 44894

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs747857317; hg19: chr15-44057632;