rs30187

Variant summary

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

The NM_001040458.3(ERAP1):​c.1583A>T​(p.Lys528Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. K528R) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Consequence

ERAP1
NM_001040458.3 missense

Scores

2
7
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.43
Variant links:
Genes affected
ERAP1 (HGNC:18173): (endoplasmic reticulum aminopeptidase 1) The protein encoded by this gene is an aminopeptidase involved in trimming HLA class I-binding precursors so that they can be presented on MHC class I molecules. The encoded protein acts as a monomer or as a heterodimer with ERAP2. This protein may also be involved in blood pressure regulation by inactivation of angiotensin II. Three transcript variants encoding two different isoforms have been found for this gene.[provided by RefSeq, Oct 2010]

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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
ERAP1NM_001040458.3 linkuse as main transcriptc.1583A>T p.Lys528Met missense_variant 11/19 ENST00000443439.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ERAP1ENST00000443439.7 linkuse as main transcriptc.1583A>T p.Lys528Met missense_variant 11/191 NM_001040458.3 P1Q9NZ08-1
ERAP1ENST00000296754.7 linkuse as main transcriptc.1583A>T p.Lys528Met missense_variant 11/201 Q9NZ08-2
ERAP1ENST00000507859.1 linkuse as main transcriptn.246A>T non_coding_transcript_exon_variant 3/52

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
55
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.22
BayesDel_addAF
Uncertain
0.030
T
BayesDel_noAF
Benign
-0.19
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.14
.;T
Eigen
Uncertain
0.62
Eigen_PC
Pathogenic
0.68
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.87
D;D
M_CAP
Benign
0.019
T
MetaRNN
Uncertain
0.54
D;D
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.3
L;L
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.61
T
PROVEAN
Uncertain
-2.9
D;D
REVEL
Benign
0.26
Sift
Benign
0.10
T;T
Sift4G
Benign
0.22
T;T
Polyphen
1.0
D;D
Vest4
0.58
MutPred
0.43
Loss of methylation at K528 (P = 0.0073);Loss of methylation at K528 (P = 0.0073);
MVP
0.29
MPC
0.48
ClinPred
0.98
D
GERP RS
6.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.60
gMVP
0.75

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: rs30187; hg19: chr5-96124330; API