rs12722051

Positions:

• chr6-32641370-A-C
• chr6-32641370-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_002122.5(HLA-DQA1):​c.143A>C​(p.Tyr48Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y48F) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 16)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DQA1	NM_002122.5	c.143A>C	p.Tyr48Ser	missense_variant	2/5	ENST00000343139.11	NP_002113.2
HLA-DQA1	XM_006715079.5	c.143A>C	p.Tyr48Ser	missense_variant	2/4		XP_006715142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-DQA1	ENST00000343139.11	c.143A>C	p.Tyr48Ser	missense_variant	2/5		NM_002122.5	ENSP00000339398	P1

Frequencies

GnomAD3 genomes Cov.: 16

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1013672 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 515282

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 16

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.062	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	8.4
DANN	Benign	0.96
DEOGEN2	Benign	0.017	.;.;T;.
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.69	.;.;T;T
M_CAP	Benign	0.0037	T
MetaRNN	Uncertain	0.55	D;D;D;D
MetaSVM	Benign	-0.96	T
MutationTaster	Benign	0.80	N;N;N;N
PrimateAI	Uncertain	0.51	T
PROVEAN	Pathogenic	-5.4	D;D;D;D
REVEL	Benign	0.15
Sift	Uncertain	0.0020	D;D;D;D
Sift4G	Uncertain	0.0040	D;D;T;D
Vest4		0.31
MutPred		0.68		Gain of disorder (P = 0.0141);Gain of disorder (P = 0.0141);Gain of disorder (P = 0.0141);Gain of disorder (P = 0.0141);
MVP		0.12
MPC		2.0
ClinPred		0.83	D
GERP RS		2.6
gMVP		0.79

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

Other links and lift over

dbSNP: rs12722051; hg19: chr6-32609147;