rs2788

Variant names:

• chr15-43772688-A-G
• rs2788
• NM_005313.5:c.*1470A>G

Variant summary

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

The NM_005313.5(PDIA3):​c.*1470A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 154,008 control chromosomes in the GnomAD database, including 2,622 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 0.16 (2614 hom., cov: 33)
  • Exomes 𝑓: 0.092 (8 hom.)
• Consequence: PDIA3 NM_005313.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42

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]

ELL3 (HGNC:23113): (elongation factor for RNA polymerase II 3) Predicted to enable cis-regulatory region sequence-specific DNA binding activity. Involved in positive regulation of transcription, DNA-templated and transcription by RNA polymerase II. Located in several cellular components, including chromosome; cytosol; and nuclear lumen. Part of transcription elongation factor complex. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000262560 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDIA3	NM_005313.5	c.*1470A>G		3_prime_UTR_variant	Exon 13 of 13	ENST00000300289.10	NP_005304.3
ELL3	NM_025165.3	c.*428T>C		3_prime_UTR_variant	Exon 11 of 11	ENST00000319359.8	NP_079441.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDIA3	ENST00000300289.10	c.*1470A>G		3_prime_UTR_variant	Exon 13 of 13	1	NM_005313.5	ENSP00000300289.5
ELL3	ENST00000319359	c.*428T>C		3_prime_UTR_variant	Exon 11 of 11	1	NM_025165.3	ENSP00000320346.3
ENSG00000262560	ENST00000417761.2	n.*1926T>C		non_coding_transcript_exon_variant	Exon 17 of 17	2		ENSP00000415219.2
ENSG00000262560	ENST00000417761.2	n.*1926T>C		3_prime_UTR_variant	Exon 17 of 17	2		ENSP00000415219.2

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24563 AN: 152170 Hom.: 2606 Cov.: 33

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.0405

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.0916

Gnomad OTH AF: 0.151

GnomAD4 exome AF: 0.0924 AC: 159 AN: 1720 Hom.: 8 Cov.: 0 AF XY: 0.0935 AC XY: 89 AN XY: 952

Gnomad4 AFR exome AF: 0.265

Gnomad4 AMR exome AF: 0.188

Gnomad4 ASJ exome AF: 0.161

Gnomad4 EAS exome AF: 0.295

Gnomad4 SAS exome AF: 0.0714

Gnomad4 FIN exome AF: 0.0221

Gnomad4 NFE exome AF: 0.0743

Gnomad4 OTH exome AF: 0.123

GnomAD4 genome AF: 0.162 AC: 24613 AN: 152288 Hom.: 2614 Cov.: 33 AF XY: 0.160 AC XY: 11897 AN XY: 74478

Gnomad4 AFR AF: 0.290

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.274

Gnomad4 SAS AF: 0.142

Gnomad4 FIN AF: 0.0405

Gnomad4 NFE AF: 0.0916

Gnomad4 OTH AF: 0.155

Alfa AF: 0.116 Hom.: 1219

Bravo AF: 0.181

Asia WGS AF: 0.207 AC: 718 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.6
DANN	Benign	0.70

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

Publications

LitVar

Other links and lift over

dbSNP: rs2788; hg19: chr15-44064886;