6-32641370-A-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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. 11/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DQA1	NM_002122.5	c.143A>T	p.Tyr48Phe	missense_variant	Exon 2 of 5	ENST00000343139.11	NP_002113.2
HLA-DQA1	XM_006715079.5	c.143A>T	p.Tyr48Phe	missense_variant	Exon 2 of 4		XP_006715142.1
HLA-DQA1-AS1	XR_007059544.1	n.-60T>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DQA1	ENST00000343139.11	c.143A>T	p.Tyr48Phe	missense_variant	Exon 2 of 5	6	NM_002122.5	ENSP00000339398.5

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

GnomAD3 exomes AF: 0.157 AC: 33759 AN: 215480 Hom.: 7584 AF XY: 0.169 AC XY: 19755 AN XY: 116908

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 SAS exome AF: 0.327

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

Gnomad4 AFR exome AF: 0.0951

Gnomad4 AMR exome AF: 0.145

Gnomad4 ASJ exome AF: 0.290

Gnomad4 EAS exome AF: 0.322

Gnomad4 SAS exome AF: 0.382

Gnomad4 FIN exome AF: 0.172

Gnomad4 NFE exome AF: 0.146

Gnomad4 OTH exome AF: 0.177

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

Gnomad4 AFR AF: 0.106

Gnomad4 AMR AF: 0.196

Gnomad4 ASJ AF: 0.299

Gnomad4 EAS AF: 0.245

Gnomad4 SAS AF: 0.398

Gnomad4 FIN AF: 0.158

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.194

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 v4.3

Name	Calibrated prediction	Score	Prediction
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;T
MetaRNN	Benign	0.0047	T;T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	0.050	N;N;N;N
REVEL	Benign	0.071
Sift	Benign	0.64	T;T;T;T
Sift4G	Benign	0.82	T;T;T;T
Vest4		0.076
MPC		0.80
ClinPred		0.0034	T
GERP RS		2.6
gMVP		0.44

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

Publications

LitVar

Other links and lift over

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