rs707949
Positions:
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_002122.5(HLA-DQA1):āc.535T>Cā(p.Phe179Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: š 0.017 ( 12 hom., cov: 16)
Exomes š: 0.095 ( 17132 hom. )
Failed GnomAD Quality Control
Consequence
HLA-DQA1
NM_002122.5 missense
NM_002122.5 missense
Scores
1
3
10
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 3.18
Genes affected
HLA-DQA1 (HGNC:4942): (major histocompatibility complex, class II, DQ alpha 1) HLA-DQA1 belongs to the HLA class II alpha chain paralogues. The class II molecule is a heterodimer consisting of an alpha (DQA) and a beta chain (DQB), both anchored in the membrane. It plays a central role in the immune system by presenting peptides derived from extracellular proteins. Class II molecules are expressed in antigen presenting cells (APC: B Lymphocytes, dendritic cells, macrophages). The alpha chain is approximately 33-35 kDa. It is encoded by 5 exons; exon 1 encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, and exon 4 encodes the transmembrane domain and the cytoplasmic tail. Within the DQ molecule both the alpha chain and the beta chain contain the polymorphisms specifying the peptide binding specificities, resulting in up to four different molecules. Typing for these polymorphisms is routinely done for bone marrow transplantation. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0016901493).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HLA-DQA1 | NM_002122.5 | c.535T>C | p.Phe179Leu | missense_variant | 3/5 | ENST00000343139.11 | |
HLA-DQA1 | XM_006715079.5 | c.535T>C | p.Phe179Leu | missense_variant | 3/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HLA-DQA1 | ENST00000343139.11 | c.535T>C | p.Phe179Leu | missense_variant | 3/5 | NM_002122.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 1478AN: 89304Hom.: 12 Cov.: 16 FAILED QC
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?
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GnomAD3 exomes AF: 0.177 AC: 36739AN: 207616Hom.: 6718 AF XY: 0.180 AC XY: 20250AN XY: 112360
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0947 AC: 105146AN: 1109920Hom.: 17132 Cov.: 32 AF XY: 0.0993 AC XY: 55081AN XY: 554592
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GnomAD4 genome ? Data not reliable, filtered out with message: AS_VQSR AF: 0.0166 AC: 1480AN: 89396Hom.: 12 Cov.: 16 AF XY: 0.0151 AC XY: 660AN XY: 43640
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Data not reliable, filtered out with message: AS_VQSR
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ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
P;P;P;P
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D
REVEL
Benign
Sift
Uncertain
D;D;D;D
Sift4G
Benign
T;T;T;T
Vest4
MutPred
Gain of catalytic residue at F179 (P = 0.052);Gain of catalytic residue at F179 (P = 0.052);Gain of catalytic residue at F179 (P = 0.052);Gain of catalytic residue at F179 (P = 0.052);
MPC
ClinPred
T
GERP RS
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