rs773736141

Variant names:

• chr15-43746571-G-A
• NM_005313.5:c.32G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-43746571-G-A
• chr15-43746571-G-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_005313.5(PDIA3):​c.32G>A​(p.Gly11Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,459,198 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: PDIA3 NM_005313.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.343

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]

CATSPER2P1 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDIA3	NM_005313.5	c.32G>A	p.Gly11Asp	missense_variant	Exon 1 of 13	ENST00000300289.10	NP_005304.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDIA3	ENST00000300289.10	c.32G>A	p.Gly11Asp	missense_variant	Exon 1 of 13	1	NM_005313.5	ENSP00000300289.5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1459198 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 725926

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.65
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.38	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.064	D
MetaRNN	Uncertain	0.67	D
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.2	L
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.23
Sift	Benign	0.13	T
Sift4G	Benign	0.29	T
Polyphen		0.0	B
Vest4		0.62
MutPred		0.63		Gain of relative solvent accessibility (P = 0.0479);
MVP		0.80
MPC		0.47
ClinPred		0.094	T
GERP RS		-0.91
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.10
gMVP		0.74

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-44038769;