ENST00000692443.1:c.177A>C

Variant names:

Variant summary

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

The ENST00000692443.1(HLA-DPA1):c.177A>C(p.Glu59Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00554 in 1,610,928 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0047 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0056 ( 42 hom. )

Consequence

HLA-DPA1
ENST00000692443.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.12

Variant links:

Genes affected

HLA-DPA1 (HGNC:4938): (major histocompatibility complex, class II, DP alpha 1) HLA-DPA1 belongs to the HLA class II alpha chain paralogues. This class II molecule is a heterodimer consisting of an alpha (DPA) and a beta (DPB) chain, 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 and its gene contains 5 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, exon 4 encodes the transmembrane domain and the cytoplasmic tail. Within the DP molecule both the alpha chain and the beta chain contain the polymorphisms specifying the peptide binding specificities, resulting in up to 4 different molecules. [provided by RefSeq, Jul 2008]

HLA-DPA1 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=0.004793346).

BP6

Variant 6-33069810-T-G is Benign according to our data. Variant chr6-33069810-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 2656480.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 42 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein
HLA-DPA1	NM_001242524.2 link	c.177A>C	p.Glu59Asp	missense_variant	Exon 3 of 6	NP_001229453.1
HLA-DPA1	NM_001242525.2 link	c.177A>C	p.Glu59Asp	missense_variant	Exon 3 of 6	NP_001229454.1
HLA-DPA1	NM_001405020.1 link	c.177A>C	p.Glu59Asp	missense_variant	Exon 2 of 4	NP_001391949.1
HLA-DPA1	NM_033554.4 link	c.177A>C	p.Glu59Asp	missense_variant	Exon 2 of 5	NP_291032.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DPA1	ENST00000692443.1 link	c.177A>C	p.Glu59Asp	missense_variant	Exon 2 of 5			ENSP00000509163.1		P20036

Frequencies

GnomAD3 genomes

AF:

0.00466

AC:

710

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00280

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00465

Gnomad ASJ

AF:

0.0242

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00579

Gnomad FIN

AF:

0.00405

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00522

Gnomad OTH

AF:

0.00527

GnomAD3 exomes

AF:

0.00540

AC:

1332

AN:

246558

Hom.:

AF XY:

0.00554

AC XY:

744

AN XY:

134412

show subpopulations

Gnomad AFR exome

AF:

0.00272

Gnomad AMR exome

AF:

0.00281

Gnomad ASJ exome

AF:

0.0236

Gnomad EAS exome

AF:

0.000602

Gnomad SAS exome

AF:

0.00813

Gnomad FIN exome

AF:

0.00518

Gnomad NFE exome

AF:

0.00502

Gnomad OTH exome

AF:

0.00543

GnomAD4 exome

AF:

0.00563

AC:

8218

AN:

1458606

Hom.:

Cov.:

AF XY:

0.00571

AC XY:

4142

AN XY:

725776

show subpopulations

Gnomad4 AFR exome

AF:

0.00365

Gnomad4 AMR exome

AF:

0.00275

Gnomad4 ASJ exome

AF:

0.0226

Gnomad4 EAS exome

AF:

0.000278

Gnomad4 SAS exome

AF:

0.00799

Gnomad4 FIN exome

AF:

0.00451

Gnomad4 NFE exome

AF:

0.00541

Gnomad4 OTH exome

AF:

0.00672

GnomAD4 genome

AF:

0.00466

AC:

710

AN:

152322

Hom.:

Cov.:

AF XY:

0.00446

AC XY:

332

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.00279

Gnomad4 AMR

AF:

0.00464

Gnomad4 ASJ

AF:

0.0242

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00580

Gnomad4 FIN

AF:

0.00405

Gnomad4 NFE

AF:

0.00522

Gnomad4 OTH

AF:

0.00522

Alfa

AF:

0.00510

Hom.:

Bravo

AF:

0.00451

TwinsUK

AF:

0.00674

AC:

ALSPAC

AF:

0.00701

AC:

ESP6500AA

AF:

0.00199

AC:

ESP6500EA

AF:

0.00535

AC:

ExAC

AF:

0.00509

AC:

598

EpiCase

AF:

0.00551

EpiControl

AF:

0.00539

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

HLA-DPA1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.57

CADD

Benign

1.1

DANN

Benign

0.96

DEOGEN2

Benign

0.0033

T;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.033

M_CAP

Benign

0.0083

MetaRNN

Benign

0.0048

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.4

L;.

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.25

N;N

REVEL

Benign

0.060

Sift

Uncertain

0.026

D;D

Sift4G

Uncertain

0.060

T;.

Polyphen

0.0

B;.

Vest4

0.16

MVP

0.014

MPC

0.43

ClinPred

0.0032

GERP RS

-5.1

Varity_R

0.22

gMVP

0.62

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

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