NM_002122.5:c.122T>C

Variant names:

• chr6-32641349-T-C
• rs1071630
• NM_002122.5:c.122T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_002122.5(HLA-DQA1):​c.122T>C​(p.Phe41Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (3842 hom., cov: 15)
  • Exomes 𝑓: 0.23 (68797 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-DQA1 NM_002122.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.905
• Publications: 57 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.1289733E-5).
• BP6: Variant 6-32641349-T-C is Benign according to our data. Variant chr6-32641349-T-C is described in ClinVar as Benign. ClinVar VariationId is 1257290.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 3842 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DQA1	NM_002122.5	MANE Select	c.122T>C	p.Phe41Ser	missense	Exon 2 of 5	NP_002113.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DQA1	ENST00000343139.11	TSL:6 MANE Select	c.122T>C	p.Phe41Ser	missense	Exon 2 of 5	ENSP00000339398.5	P01909
	HLA-DQA1	ENST00000374949.2	TSL:6	c.122T>C	p.Phe41Ser	missense	Exon 2 of 4	ENSP00000364087.2	P01909
	HLA-DQA1	ENST00000395363.5	TSL:6	c.122T>C	p.Phe41Ser	missense	Exon 2 of 5	ENSP00000378767.1	P01909

Frequencies

GnomAD3 genomes AF: 0.228 AC: 18563 AN: 81386 Hom.: 3838 Cov.: 15

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.240

GnomAD2 exomes AF: 0.493 AC: 92599 AN: 187738 AF XY: 0.494

Gnomad AFR exome AF: 0.415

Gnomad AMR exome AF: 0.668

Gnomad ASJ exome AF: 0.551

Gnomad EAS exome AF: 0.449

Gnomad FIN exome AF: 0.403

Gnomad NFE exome AF: 0.495

Gnomad OTH exome AF: 0.450

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.232 AC: 192749 AN: 831528 Hom.: 68797 Cov.: 25 AF XY: 0.247 AC XY: 104198 AN XY: 422096

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.178 AC: 3712 AN: 20892

American (AMR) AF: 0.534 AC: 14571 AN: 27306

Ashkenazi Jewish (ASJ) AF: 0.330 AC: 4917 AN: 14912

East Asian (EAS) AF: 0.129 AC: 3337 AN: 25792

South Asian (SAS) AF: 0.358 AC: 20903 AN: 58394

European-Finnish (FIN) AF: 0.197 AC: 7571 AN: 38386

Middle Eastern (MID) AF: 0.387 AC: 1327 AN: 3432

European-Non Finnish (NFE) AF: 0.213 AC: 129335 AN: 607798

Other (OTH) AF: 0.204 AC: 7076 AN: 34616

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.228 AC: 18572 AN: 81452 Hom.: 3842 Cov.: 15 AF XY: 0.225 AC XY: 8955 AN XY: 39856

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.190 AC: 4363 AN: 22966

American (AMR) AF: 0.197 AC: 1272 AN: 6472

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 523 AN: 1794

East Asian (EAS) AF: 0.146 AC: 356 AN: 2446

South Asian (SAS) AF: 0.202 AC: 536 AN: 2648

European-Finnish (FIN) AF: 0.118 AC: 682 AN: 5762

Middle Eastern (MID) AF: 0.333 AC: 38 AN: 114

European-Non Finnish (NFE) AF: 0.276 AC: 10368 AN: 37620

Other (OTH) AF: 0.235 AC: 256 AN: 1088

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.580 Hom.: 67706

ESP6500AA AF: 0.388 AC: 1711

ESP6500EA AF: 0.441 AC: 3781

ExAC AF: 0.555 AC: 67214

Asia WGS AF: 0.469 AC: 1583 AN: 3376

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.049
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	5.3
DANN	Benign	0.15
DEOGEN2	Benign	0.0032	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0013	N
LIST_S2	Benign	0.34	T
MetaRNN	Benign	0.000011	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.91
PrimateAI	Benign	0.41	T
PROVEAN	Benign	3.1	N
REVEL	Uncertain	0.29
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Vest4		0.040
MPC		1.4
ClinPred		0.000028	T
GERP RS		3.0
gMVP		0.60
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1071630; hg19: chr6-32609126; COSMIC: COSV58239937; COSMIC: COSV58239937;