3-123092361-C-T
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_006810.4(PDIA5):c.176C>T(p.Ala59Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,510 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: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
PDIA5
NM_006810.4 missense
NM_006810.4 missense
Scores
1
4
14
Clinical Significance
Conservation
PhyloP100: 6.07
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=0.3843544).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PDIA5 | NM_006810.4 | c.176C>T | p.Ala59Val | missense_variant | 3/17 | ENST00000316218.12 | NP_006801.1 | |
PDIA5 | NR_028444.2 | n.316C>T | non_coding_transcript_exon_variant | 3/16 | ||||
PDIA5 | XR_007095629.1 | n.316C>T | non_coding_transcript_exon_variant | 3/14 | ||||
PDIA5 | XR_007095630.1 | n.316C>T | non_coding_transcript_exon_variant | 3/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PDIA5 | ENST00000316218.12 | c.176C>T | p.Ala59Val | missense_variant | 3/17 | 1 | NM_006810.4 | ENSP00000323313.7 | ||
PDIA5 | ENST00000489923.5 | n.176C>T | non_coding_transcript_exon_variant | 3/16 | 1 | ENSP00000417520.1 | ||||
PDIA5 | ENST00000484644 | c.-113C>T | 5_prime_UTR_variant | 3/6 | 5 | ENSP00000419946.1 | ||||
PDIA5 | ENST00000495004.1 | n.195C>T | non_coding_transcript_exon_variant | 2/6 | 3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1460510Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726610
GnomAD4 exome
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2
AN:
1460510
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Cov.:
31
AF XY:
AC XY:
1
AN XY:
726610
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
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 | Oct 02, 2023 | The c.176C>T (p.A59V) alteration is located in exon 3 (coding exon 3) of the PDIA5 gene. This alteration results from a C to T substitution at nucleotide position 176, causing the alanine (A) at amino acid position 59 to be replaced by a valine (V). 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
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
D
Sift4G
Benign
T
Polyphen
D
Vest4
MutPred
Loss of sheet (P = 0.0011);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.