NM_174924.2:c.681+29A>G

Variant names:

• chr16-20374793-T-C
• rs4522429
• NM_174924.2:c.681+29A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.905 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDILT	NM_174924.2	MANE Select	c.681+29A>G		intron	N/A	NP_777584.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDILT	ENST00000302451.9	TSL:1 MANE Select	c.681+29A>G		intron	N/A	ENSP00000305465.4

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

GnomAD2 exomes AF: 0.795 AC: 189341 AN: 238130 AF XY: 0.809

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 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

African (AFR) AF: 0.687 AC: 22531 AN: 32778

American (AMR) AF: 0.668 AC: 27951 AN: 41856

Ashkenazi Jewish (ASJ) AF: 0.869 AC: 21807 AN: 25094

East Asian (EAS) AF: 0.339 AC: 13389 AN: 39458

South Asian (SAS) AF: 0.808 AC: 66775 AN: 82662

European-Finnish (FIN) AF: 0.873 AC: 46270 AN: 52980

Middle Eastern (MID) AF: 0.844 AC: 4789 AN: 5674

European-Non Finnish (NFE) AF: 0.915 AC: 1009386 AN: 1102670

Other (OTH) AF: 0.845 AC: 50415 AN: 59688

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

African (AFR) AF: 0.686 AC: 28462 AN: 41476

American (AMR) AF: 0.744 AC: 11381 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.873 AC: 3030 AN: 3470

East Asian (EAS) AF: 0.344 AC: 1775 AN: 5162

South Asian (SAS) AF: 0.775 AC: 3730 AN: 4816

European-Finnish (FIN) AF: 0.854 AC: 9039 AN: 10584

Middle Eastern (MID) AF: 0.857 AC: 252 AN: 294

European-Non Finnish (NFE) AF: 0.911 AC: 61945 AN: 68010

Other (OTH) AF: 0.801 AC: 1690 AN: 2110

Alfa AF: 0.872 Hom.: 100889

Bravo AF: 0.784

Asia WGS AF: 0.548 AC: 1911 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.41
DANN	Benign	0.32
PhyloP100		-1.6
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: rs4522429; hg19: chr16-20386115; COSMIC: COSV56700476;