chr16-20362428-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_174924.2(PDILT):c.1392G>C(p.Arg464Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,614,044 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000018 ( 0 hom. )
Consequence
PDILT
NM_174924.2 missense
NM_174924.2 missense
Scores
1
6
12
Clinical Significance
Conservation
PhyloP100: -0.584
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PDILT | NM_174924.2 | c.1392G>C | p.Arg464Ser | missense_variant | 10/12 | ENST00000302451.9 | |
PDILT | XM_011545766.4 | c.570G>C | p.Arg190Ser | missense_variant | 6/8 | ||
PDILT | XM_011545765.2 | c.*40-1771G>C | intron_variant | ||||
PDILT | XR_950754.2 | n.1487-1771G>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PDILT | ENST00000302451.9 | c.1392G>C | p.Arg464Ser | missense_variant | 10/12 | 1 | NM_174924.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152202Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251308Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135816
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GnomAD4 exome AF: 0.0000178 AC: 26AN: 1461842Hom.: 0 Cov.: 31 AF XY: 0.0000179 AC XY: 13AN XY: 727214
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152202Hom.: 0 Cov.: 31 AF XY: 0.0000134 AC XY: 1AN XY: 74354
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 01, 2022 | The c.1392G>C (p.R464S) alteration is located in exon 10 (coding exon 9) of the PDILT gene. This alteration results from a G to C substitution at nucleotide position 1392, causing the arginine (R) at amino acid position 464 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
N
PrimateAI
Benign
T
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
P
Vest4
MutPred
Loss of methylation at R464 (P = 0.0533);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at