rs12446492

chr16-20397055-T-A

Variant summary

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

The NM_174924.2(PDILT):c.202+2044A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.483 in 152,142 control chromosomes in the GnomAD database, including 18,311 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 0.48 (18311 hom., cov: 33)
• Consequence: PDILT NM_174924.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.727

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.791 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDILT	NM_174924.2	c.202+2044A>T		intron_variant		ENST00000302451.9
PDILT	XM_011545764.2	c.202+2044A>T		intron_variant
PDILT	XM_011545765.2	c.202+2044A>T		intron_variant
PDILT	XR_950754.2	n.451+2044A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDILT	ENST00000302451.9	c.202+2044A>T		intron_variant		1	NM_174924.2	P1
PDILT	ENST00000575561.1	c.202+2044A>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.483 AC: 73393 AN: 152024 Hom.: 18283 Cov.: 33

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.568

Gnomad ASJ AF: 0.434

Gnomad EAS AF: 0.811

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.487

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.483 AC: 73477 AN: 152142 Hom.: 18311 Cov.: 33 AF XY: 0.488 AC XY: 36274 AN XY: 74396

Gnomad4 AFR AF: 0.509

Gnomad4 AMR AF: 0.568

Gnomad4 ASJ AF: 0.434

Gnomad4 EAS AF: 0.811

Gnomad4 SAS AF: 0.570

Gnomad4 FIN AF: 0.405

Gnomad4 NFE AF: 0.431

Gnomad4 OTH AF: 0.487

Alfa AF: 0.455 Hom.: 2027

Bravo AF: 0.499

Asia WGS AF: 0.689 AC: 2400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.97
Dann	Benign	0.79

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: rs12446492; hg19: chr16-20408377;