rs556623443
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PP3_ModerateBP6
The NM_001040458.3(ERAP1):āc.955A>Gā(p.Met319Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,614,162 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).
Frequency
Genomes: š 0.000026 ( 0 hom., cov: 31)
Exomes š: 0.000024 ( 0 hom. )
Consequence
ERAP1
NM_001040458.3 missense
NM_001040458.3 missense
Scores
12
3
3
Clinical Significance
Conservation
PhyloP100: 8.02
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 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.897
BP6
?
Variant 5-96793922-T-C is Benign according to our data. Variant chr5-96793922-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 207936.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ERAP1 | NM_001040458.3 | c.955A>G | p.Met319Val | missense_variant | 6/19 | ENST00000443439.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ERAP1 | ENST00000443439.7 | c.955A>G | p.Met319Val | missense_variant | 6/19 | 1 | NM_001040458.3 | P1 | |
ERAP1 | ENST00000296754.7 | c.955A>G | p.Met319Val | missense_variant | 6/20 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152192Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000637 AC: 16AN: 251334Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135828
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GnomAD4 exome AF: 0.0000239 AC: 35AN: 1461852Hom.: 0 Cov.: 33 AF XY: 0.0000206 AC XY: 15AN XY: 727232
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152310Hom.: 0 Cov.: 31 AF XY: 0.0000268 AC XY: 2AN XY: 74488
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Long QT syndrome Benign:1
Likely benign, no assertion criteria provided | research | Medical Research Institute, Tokyo Medical and Dental University | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
H;H
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
T
PROVEAN
Uncertain
D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;D
Vest4
MutPred
Gain of helix (P = 0.2684);Gain of helix (P = 0.2684);
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