6-32642175-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_002122.5(HLA-DQA1):ā€‹c.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

Scores

1
3
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.18
Variant links:
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]

Genome browser will be placed here

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 Protein UniProt
HLA-DQA1NM_002122.5 linkuse as main transcriptc.535T>C p.Phe179Leu missense_variant 3/5 ENST00000343139.11 NP_002113.2
HLA-DQA1XM_006715079.5 linkuse as main transcriptc.535T>C p.Phe179Leu missense_variant 3/4 XP_006715142.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
HLA-DQA1ENST00000343139.11 linkuse as main transcriptc.535T>C p.Phe179Leu missense_variant 3/5 NM_002122.5 ENSP00000339398 P1

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
1478
AN:
89304
Hom.:
12
Cov.:
16
FAILED QC
Gnomad AFR
AF:
0.0135
Gnomad AMI
AF:
0.00680
Gnomad AMR
AF:
0.0167
Gnomad ASJ
AF:
0.0251
Gnomad EAS
AF:
0.00830
Gnomad SAS
AF:
0.0145
Gnomad FIN
AF:
0.00748
Gnomad MID
AF:
0.00806
Gnomad NFE
AF:
0.0207
Gnomad OTH
AF:
0.0106
GnomAD3 exomes
AF:
0.177
AC:
36739
AN:
207616
Hom.:
6718
AF XY:
0.180
AC XY:
20250
AN XY:
112360
show subpopulations
Gnomad AFR exome
AF:
0.129
Gnomad AMR exome
AF:
0.216
Gnomad ASJ exome
AF:
0.255
Gnomad EAS exome
AF:
0.129
Gnomad SAS exome
AF:
0.202
Gnomad FIN exome
AF:
0.110
Gnomad NFE exome
AF:
0.178
Gnomad OTH exome
AF:
0.185
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0947
AC:
105146
AN:
1109920
Hom.:
17132
Cov.:
32
AF XY:
0.0993
AC XY:
55081
AN XY:
554592
show subpopulations
Gnomad4 AFR exome
AF:
0.0690
Gnomad4 AMR exome
AF:
0.176
Gnomad4 ASJ exome
AF:
0.158
Gnomad4 EAS exome
AF:
0.0550
Gnomad4 SAS exome
AF:
0.154
Gnomad4 FIN exome
AF:
0.0602
Gnomad4 NFE exome
AF:
0.0887
Gnomad4 OTH exome
AF:
0.0945
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0166
AC:
1480
AN:
89396
Hom.:
12
Cov.:
16
AF XY:
0.0151
AC XY:
660
AN XY:
43640
show subpopulations
Gnomad4 AFR
AF:
0.0135
Gnomad4 AMR
AF:
0.0167
Gnomad4 ASJ
AF:
0.0251
Gnomad4 EAS
AF:
0.00832
Gnomad4 SAS
AF:
0.0148
Gnomad4 FIN
AF:
0.00748
Gnomad4 NFE
AF:
0.0207
Gnomad4 OTH
AF:
0.0105
Alfa
AF:
0.199
Hom.:
773
ExAC
AF:
0.209
AC:
24496

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.55
T
BayesDel_noAF
Benign
-0.42
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.025
.;.;T;.
Eigen
Benign
0.022
Eigen_PC
Benign
0.13
FATHMM_MKL
Benign
0.75
D
LIST_S2
Benign
0.78
.;.;T;T
MetaRNN
Benign
0.0017
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
0.00040
P;P;P;P
PrimateAI
Uncertain
0.64
T
PROVEAN
Pathogenic
-5.0
D;D;D;D
REVEL
Benign
0.19
Sift
Uncertain
0.025
D;D;D;D
Sift4G
Benign
0.068
T;T;T;T
Vest4
0.28
MutPred
0.87
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
1.1
ClinPred
0.040
T
GERP RS
4.1
gMVP
0.87

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: rs707949; hg19: chr6-32609952; COSMIC: COSV58237320; COSMIC: COSV58237320; API