16-20374793-T-C

Variant summary

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

The NM_174924.2(PDILT):c.681+29A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.869 in 1,594,980 control chromosomes in the GnomAD database, including 612,705 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 0.80 (50374 hom., cov: 31)
  • Exomes 𝑓: 0.88 (562331 hom.)
• Consequence: PDILT NM_174924.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.63

Genes affected

PDILT (HGNC:27338): (protein disulfide isomerase like, testis expressed) 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 has an N-terminal ER-signal sequence, two thioredoxin (TRX) domains with non-classical Ser-Lys-Gln-Ser and Ser-Lys-Lys-Cys motifs, respectively, two TRX-like domains, and a C-terminal ER-retention sequence. The protein lacks oxidoreductase activity in vitro and probably functions as a chaperone. This gene's expression appears to be limited to the testis. [provided by RefSeq, Dec 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.905 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDILT	NM_174924.2	c.681+29A>G		intron_variant		ENST00000302451.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDILT	ENST00000302451.9	c.681+29A>G		intron_variant		1	NM_174924.2	P1

Frequencies

GnomAD3 genomes AF: 0.803 AC: 122068 AN: 152002 Hom.: 50359 Cov.: 31

Gnomad AFR AF: 0.687

Gnomad AMI AF: 0.902

Gnomad AMR AF: 0.745

Gnomad ASJ AF: 0.873

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.774

Gnomad FIN AF: 0.854

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.911

Gnomad OTH AF: 0.802

GnomAD3 exomes AF: 0.795 AC: 189341 AN: 238130 Hom.: 78754 AF XY: 0.809 AC XY: 103725 AN XY: 128274

Gnomad AFR exome AF: 0.680

Gnomad AMR exome AF: 0.656

Gnomad ASJ exome AF: 0.869

Gnomad EAS exome AF: 0.327

Gnomad SAS exome AF: 0.801

Gnomad FIN exome AF: 0.863

Gnomad NFE exome AF: 0.907

Gnomad OTH exome AF: 0.835

GnomAD4 exome AF: 0.876 AC: 1263313 AN: 1442860 Hom.: 562331 Cov.: 36 AF XY: 0.875 AC XY: 626735 AN XY: 715958

Gnomad4 AFR exome AF: 0.687

Gnomad4 AMR exome AF: 0.668

Gnomad4 ASJ exome AF: 0.869

Gnomad4 EAS exome AF: 0.339

Gnomad4 SAS exome AF: 0.808

Gnomad4 FIN exome AF: 0.873

Gnomad4 NFE exome AF: 0.915

Gnomad4 OTH exome AF: 0.845

GnomAD4 genome AF: 0.803 AC: 122125 AN: 152120 Hom.: 50374 Cov.: 31 AF XY: 0.795 AC XY: 59127 AN XY: 74370

Gnomad4 AFR AF: 0.686

Gnomad4 AMR AF: 0.744

Gnomad4 ASJ AF: 0.873

Gnomad4 EAS AF: 0.344

Gnomad4 SAS AF: 0.775

Gnomad4 FIN AF: 0.854

Gnomad4 NFE AF: 0.911

Gnomad4 OTH AF: 0.801

Alfa AF: 0.879 Hom.: 81683

Bravo AF: 0.784

Asia WGS AF: 0.548 AC: 1911 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.41
Dann	Benign	0.32

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: rs4522429; hg19: chr16-20386115; COSMIC: COSV56700476;