NM_002122.5:c.143A>T

Variant names:

• chr6-32641370-A-T
• rs12722051
• NM_002122.5:c.143A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002122.5(HLA-DQA1):​c.143A>T​(p.Tyr48Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 1,079,022 control chromosomes in the GnomAD database, including 55,683 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.17 (3948 hom., cov: 16)
  • Exomes 𝑓: 0.17 (51735 hom.)
• Consequence: HLA-DQA1 NM_002122.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.275
• Publications: 36 publications found

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]

HLA-DQA1-AS1 (HGNC:56667): (HLA-DQA1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0047302544).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002122.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DQA1	NM_002122.5	MANE Select	c.143A>T	p.Tyr48Phe	missense	Exon 2 of 5	NP_002113.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DQA1	ENST00000343139.11	TSL:6 MANE Select	c.143A>T	p.Tyr48Phe	missense	Exon 2 of 5	ENSP00000339398.5
	HLA-DQA1	ENST00000374949.2	TSL:6	c.143A>T	p.Tyr48Phe	missense	Exon 2 of 4	ENSP00000364087.2
	HLA-DQA1	ENST00000395363.5	TSL:6	c.143A>T	p.Tyr48Phe	missense	Exon 2 of 5	ENSP00000378767.1

Frequencies

GnomAD3 genomes AF: 0.169 AC: 16488 AN: 97430 Hom.: 3953 Cov.: 16

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.167

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.198

GnomAD2 exomes AF: 0.157 AC: 33759 AN: 215480 AF XY: 0.169

Gnomad AFR exome AF: 0.0831

Gnomad AMR exome AF: 0.0874

Gnomad ASJ exome AF: 0.221

Gnomad EAS exome AF: 0.193

Gnomad FIN exome AF: 0.128

Gnomad NFE exome AF: 0.135

Gnomad OTH exome AF: 0.156

GnomAD4 exome AF: 0.172 AC: 169011 AN: 981496 Hom.: 51735 Cov.: 23 AF XY: 0.182 AC XY: 90797 AN XY: 497638

African (AFR) AF: 0.0951 AC: 2395 AN: 25174

American (AMR) AF: 0.145 AC: 4523 AN: 31108

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 5297 AN: 18242

East Asian (EAS) AF: 0.322 AC: 9057 AN: 28114

South Asian (SAS) AF: 0.382 AC: 27446 AN: 71942

European-Finnish (FIN) AF: 0.172 AC: 7433 AN: 43172

Middle Eastern (MID) AF: 0.205 AC: 799 AN: 3906

European-Non Finnish (NFE) AF: 0.146 AC: 104774 AN: 718632

Other (OTH) AF: 0.177 AC: 7287 AN: 41206

GnomAD4 genome AF: 0.169 AC: 16485 AN: 97526 Hom.: 3948 Cov.: 16 AF XY: 0.173 AC XY: 8241 AN XY: 47592

African (AFR) AF: 0.106 AC: 2945 AN: 27864

American (AMR) AF: 0.196 AC: 1545 AN: 7892

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 648 AN: 2164

East Asian (EAS) AF: 0.245 AC: 708 AN: 2894

South Asian (SAS) AF: 0.398 AC: 1201 AN: 3016

European-Finnish (FIN) AF: 0.158 AC: 1105 AN: 7006

Middle Eastern (MID) AF: 0.157 AC: 26 AN: 166

European-Non Finnish (NFE) AF: 0.178 AC: 7958 AN: 44632

Other (OTH) AF: 0.194 AC: 254 AN: 1312

Alfa AF: 0.188 Hom.: 829

ESP6500AA AF: 0.0962 AC: 424

ESP6500EA AF: 0.167 AC: 1429

ExAC AF: 0.187 AC: 22593

Asia WGS AF: 0.225 AC: 755 AN: 3374

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	0.0080
DANN	Benign	0.22
DEOGEN2	Benign	0.0036	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.085	N
LIST_S2	Benign	0.50	T
MetaRNN	Benign	0.0047	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.28
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	0.050	N
REVEL	Benign	0.071
Sift	Benign	0.64	T
Sift4G	Benign	0.82	T
Vest4		0.076
MPC		0.80
ClinPred		0.0034	T
GERP RS		2.6
gMVP		0.44
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12722051; hg19: chr6-32609147; COSMIC: COSV58237512; COSMIC: COSV58237512;