rs11864909

Variant names:

• chr16-20389517-C-T
• rs11864909
• NM_174924.2:c.203-4666G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_174924.2(PDILT):​c.203-4666G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 151,996 control chromosomes in the GnomAD database, including 4,444 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 0.23 (4444 hom., cov: 32)
• Consequence: PDILT NM_174924.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.281
• Publications: 32 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]

ENSG00000263237 (HGNC:58553):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDILT	NM_174924.2	c.203-4666G>A		intron_variant	Intron 2 of 11	ENST00000302451.9	NP_777584.1
PDILT	XM_011545764.2	c.203-4666G>A		intron_variant	Intron 2 of 9		XP_011544066.1
PDILT	XM_011545765.2	c.203-4666G>A		intron_variant	Intron 2 of 9		XP_011544067.1
PDILT	XR_950754.2	n.452-4666G>A		intron_variant	Intron 2 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDILT	ENST00000302451.9	c.203-4666G>A		intron_variant	Intron 2 of 11	1	NM_174924.2	ENSP00000305465.4
PDILT	ENST00000575561.1	c.203-608G>A		intron_variant	Intron 2 of 3	5		ENSP00000459161.1
ENSG00000263237	ENST00000577173.1	n.59-1091C>T		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34513 AN: 151878 Hom.: 4441 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.227 AC: 34518 AN: 151996 Hom.: 4444 Cov.: 32 AF XY: 0.228 AC XY: 16953 AN XY: 74280

African (AFR) AF: 0.103 AC: 4267 AN: 41488

American (AMR) AF: 0.274 AC: 4191 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 811 AN: 3470

East Asian (EAS) AF: 0.141 AC: 728 AN: 5162

South Asian (SAS) AF: 0.294 AC: 1415 AN: 4808

European-Finnish (FIN) AF: 0.292 AC: 3085 AN: 10552

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.282 AC: 19168 AN: 67934

Other (OTH) AF: 0.229 AC: 483 AN: 2112

Alfa AF: 0.267 Hom.: 22880

Bravo AF: 0.219

Asia WGS AF: 0.211 AC: 735 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.7
DANN	Benign	0.55
PhyloP100		0.28
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: rs11864909; hg19: chr16-20400839;