chr3-123150248-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_006810.4(PDIA5):c.1157C>T(p.Pro386Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000155 in 1,612,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000016 ( 0 hom. )
Consequence
PDIA5
NM_006810.4 missense
NM_006810.4 missense
Scores
2
7
10
Clinical Significance
Conservation
PhyloP100: 4.42
Genes affected
PDIA5 (HGNC:24811): (protein disulfide isomerase family A member 5) 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 an N-terminal ER-signal sequence, three catalytically active thioredoxin (TRX) domains, a TRX-like domain, and a C-terminal ER-retention sequence. The N-terminal TRX-like domain is the primary binding site for the major ER chaperone calreticulin and possibly other proteins and substrates as well. Alternative splicing results in multiple protein- and non-protein-coding transcript variants. [provided by RefSeq, Dec 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.30985245).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PDIA5 | NM_006810.4 | c.1157C>T | p.Pro386Leu | missense_variant | 14/17 | ENST00000316218.12 | |
PDIA5 | NR_028444.2 | n.1141C>T | non_coding_transcript_exon_variant | 13/16 | |||
PDIA5 | XR_007095629.1 | n.1278C>T | non_coding_transcript_exon_variant | 14/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PDIA5 | ENST00000316218.12 | c.1157C>T | p.Pro386Leu | missense_variant | 14/17 | 1 | NM_006810.4 | P1 | |
PDIA5 | ENST00000489923.5 | c.*212C>T | 3_prime_UTR_variant, NMD_transcript_variant | 13/16 | 1 | ||||
PDIA5 | ENST00000467157.1 | n.1262C>T | non_coding_transcript_exon_variant | 3/5 | 2 | ||||
PDIA5 | ENST00000485208.1 | n.382C>T | non_coding_transcript_exon_variant | 4/4 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152150Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000240 AC: 6AN: 249682Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135274
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GnomAD4 exome AF: 0.0000164 AC: 24AN: 1460522Hom.: 0 Cov.: 30 AF XY: 0.0000138 AC XY: 10AN XY: 726638
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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 | Jan 04, 2022 | The c.1157C>T (p.P386L) alteration is located in exon 14 (coding exon 14) of the PDIA5 gene. This alteration results from a C to T substitution at nucleotide position 1157, causing the proline (P) at amino acid position 386 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Benign
Sift
Benign
D
Sift4G
Uncertain
D
Polyphen
B
Vest4
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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