rs12446492

Variant names:

• chr16-20397055-T-A
• rs12446492
• NM_174924.2:c.202+2044A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174924.2. 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
	PDILT	NM_174924.2	MANE Select	c.202+2044A>T		intron	N/A	NP_777584.1	Q8N807

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDILT	ENST00000302451.9	TSL:1 MANE Select	c.202+2044A>T		intron	N/A	ENSP00000305465.4	Q8N807
	PDILT	ENST00000575561.1	TSL:5	c.202+2044A>T		intron	N/A	ENSP00000459161.1	I3L1W7

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

African (AFR) AF: 0.509 AC: 21128 AN: 41500

American (AMR) AF: 0.568 AC: 8688 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.434 AC: 1505 AN: 3468

East Asian (EAS) AF: 0.811 AC: 4203 AN: 5180

South Asian (SAS) AF: 0.570 AC: 2748 AN: 4818

European-Finnish (FIN) AF: 0.405 AC: 4288 AN: 10582

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.431 AC: 29332 AN: 67984

Other (OTH) AF: 0.487 AC: 1030 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.97
DANN	Benign	0.79
PhyloP100		-0.73
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12446492; hg19: chr16-20408377;