16-20360573-C-T

Variant names:

• chr16-20360573-C-T
• rs773034409
• NM_174924.2:c.1501G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_174924.2(PDILT):​c.1501G>A​(p.Asp501Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,460,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D501Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: PDILT NM_174924.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.51

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13129124).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDILT	NM_174924.2	c.1501G>A	p.Asp501Asn	missense_variant	Exon 11 of 12	ENST00000302451.9	NP_777584.1
PDILT	XM_011545766.4	c.679G>A	p.Asp227Asn	missense_variant	Exon 7 of 8		XP_011544068.1
PDILT	XR_950754.2	n.1571G>A		non_coding_transcript_exon_variant	Exon 10 of 11
PDILT	XM_011545765.2	c.*124G>A		downstream_gene_variant			XP_011544067.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDILT	ENST00000302451.9	c.1501G>A	p.Asp501Asn	missense_variant	Exon 11 of 12	1	NM_174924.2	ENSP00000305465.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251424 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135874

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1460792 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 726806

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.2	L
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.080
Sift	Uncertain	0.024	D
Sift4G	Benign	0.11	T
Polyphen		0.65	P
Vest4		0.23
MutPred		0.28		Loss of sheet (P = 0.0228);
MVP		0.23
MPC		0.068
ClinPred		0.25	T
GERP RS		3.6
Varity_R		0.11
gMVP		0.24

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: rs773034409; hg19: chr16-20371895;