12-112013565-C-T

Variant summary

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

The NM_006817.4(ERP29):​c.100C>T​(p.His34Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000013 in 1,611,312 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: 33)
Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

ERP29
NM_006817.4 missense

Scores

1
9
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.78
Variant links:
Genes affected
ERP29 (HGNC:13799): (endoplasmic reticulum protein 29) This gene encodes a protein which localizes to the lumen of the endoplasmic reticulum (ER). It is a member of the protein disulfide isomerase (PDI) protein family but lacks an active thioredoxin motif, suggesting that this protein does not function as a disulfide isomerase. The canonical protein dimerizes and is thought to play a role in the processing of secretory proteins within the ER. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2016]

Genome browser will be placed here

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 rank MANE Protein UniProt
ERP29NM_006817.4 linkc.100C>T p.His34Tyr missense_variant Exon 1 of 3 ENST00000261735.4 NP_006808.1 P30040-1V9HW71
ERP29NM_001034025.2 linkc.100C>T p.His34Tyr missense_variant Exon 1 of 2 NP_001029197.1 P30040-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ERP29ENST00000261735.4 linkc.100C>T p.His34Tyr missense_variant Exon 1 of 3 1 NM_006817.4 ENSP00000261735.3 P30040-1
ERP29ENST00000553161.1 linkn.137C>T non_coding_transcript_exon_variant Exon 1 of 2 1
ERP29ENST00000455836.1 linkc.100C>T p.His34Tyr missense_variant Exon 1 of 2 2 ENSP00000412083.1 P30040-2
ERP29ENST00000552052.1 linkc.84C>T p.Cys28Cys synonymous_variant Exon 1 of 2 3 ENSP00000447472.1 F8W1G0

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152242
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000137
AC:
20
AN:
1459070
Hom.:
0
Cov.:
31
AF XY:
0.0000124
AC XY:
9
AN XY:
725882
show subpopulations
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:
0.0000171
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152242
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74384
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
May 08, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.100C>T (p.H34Y) alteration is located in exon 1 (coding exon 1) of the ERP29 gene. This alteration results from a C to T substitution at nucleotide position 100, causing the histidine (H) at amino acid position 34 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.40
BayesDel_addAF
Uncertain
0.10
D
BayesDel_noAF
Benign
-0.090
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.17
T;.
Eigen
Uncertain
0.47
Eigen_PC
Uncertain
0.48
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.85
D;T
M_CAP
Benign
0.023
T
MetaRNN
Uncertain
0.54
D;D
MetaSVM
Benign
-0.47
T
MutationAssessor
Uncertain
2.0
M;M
PrimateAI
Uncertain
0.77
T
PROVEAN
Benign
-1.3
N;D
REVEL
Uncertain
0.54
Sift
Benign
0.23
T;D
Sift4G
Benign
0.089
T;D
Polyphen
0.88
P;.
Vest4
0.52
MutPred
0.61
Loss of disorder (P = 0.0393);Loss of disorder (P = 0.0393);
MVP
0.47
MPC
0.23
ClinPred
0.95
D
GERP RS
4.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.47
gMVP
0.52

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs886272772; hg19: chr12-112451369; API