6-32637511-T-C

Position:

chr6-32637511-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_002122.5(HLA-DQA1):c.53T>C(p.Met18Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00135 in 1,169,610 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.00028 ( 1 hom., cov: 15)

Exomes 𝑓: 0.0015 ( 20 hom. )

Consequence

HLA-DQA1
NM_002122.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.01

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]

HLA-DQA1 links:

HLA-DQA1-AS1 (HGNC:):

HLA-DQA1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0029515028).

BP6

Variant 6-32637511-T-C is Benign according to our data. Variant chr6-32637511-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3341556.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
HLA-DQA1	NM_002122.5 linkuse as main transcript	c.53T>C	p.Met18Thr	missense_variant	1/5	ENST00000343139.11	NP_002113.2
HLA-DQA1-AS1	XR_007059544.1 linkuse as main transcript	n.2652A>G		non_coding_transcript_exon_variant	2/2
HLA-DQA1	XM_006715079.5 linkuse as main transcript	c.53T>C	p.Met18Thr	missense_variant	1/4		XP_006715142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-DQA1	ENST00000343139.11 linkuse as main transcript	c.53T>C	p.Met18Thr	missense_variant	1/5		NM_002122.5	ENSP00000339398	P1

Frequencies

GnomAD3 genomes

AF:

0.000278

AC:

AN:

100650

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00160

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00330

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00122

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000179

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0187

AC:

4530

AN:

241770

Hom.:

333

AF XY:

0.0180

AC XY:

2348

AN XY:

130666

show subpopulations

Gnomad AFR exome

AF:

0.00180

Gnomad AMR exome

AF:

0.00486

Gnomad ASJ exome

AF:

0.00317

Gnomad EAS exome

AF:

0.124

Gnomad SAS exome

AF:

0.00842

Gnomad FIN exome

AF:

0.0433

Gnomad NFE exome

AF:

0.00918

Gnomad OTH exome

AF:

0.0111

GnomAD4 exome

AF:

0.00145

AC:

1554

AN:

1068858

Hom.:

Cov.:

AF XY:

0.00155

AC XY:

834

AN XY:

538524

show subpopulations

Gnomad4 AFR exome

AF:

0.000279

Gnomad4 AMR exome

AF:

0.00156

Gnomad4 ASJ exome

AF:

0.000835

Gnomad4 EAS exome

AF:

0.00771

Gnomad4 SAS exome

AF:

0.00162

Gnomad4 FIN exome

AF:

0.00361

Gnomad4 NFE exome

AF:

0.00117

Gnomad4 OTH exome

AF:

0.00111

GnomAD4 genome

AF:

0.000278

AC:

AN:

100752

Hom.:

Cov.:

AF XY:

0.000285

AC XY:

AN XY:

49154

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00331

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00122

Gnomad4 NFE

AF:

0.000179

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00777

Hom.:

TwinsUK

AF:

0.0119

AC:

ALSPAC

AF:

0.0127

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00895

AC:

ExAC

AF:

0.0204

AC:

2482

Asia WGS

AF:

0.0430

AC:

151

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2024

HLA-DQA1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.55

DEOGEN2

Benign

0.033

.;.;.;T;.

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.65

T;.;.;T;T

MetaRNN

Benign

0.0030

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.37

PROVEAN

Pathogenic

-5.5

D;N;N;N;N

REVEL

Benign

0.23

Sift

Benign

0.053

.;T;T;D;T

Sift4G

Pathogenic

0.0

D;D;D;D;D

Vest4

0.092, 0.14, 0.10

MPC

0.96

ClinPred

0.0093

GERP RS

3.0

gMVP

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over