Genetic Variant NM_002116.8:c.502A>T (chr6-29943426-A-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_002116.8(HLA-A):c.502A>T(p.Lys168*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 5)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HLA-A
NM_002116.8 stop_gained

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.509

Publications

29 publications found

Variant links:

Genes affected

HLA-A (HGNC:4931): (major histocompatibility complex, class I, A) HLA-A belongs to the HLA class I heavy chain paralogues. This class I molecule is a heterodimer consisting of a heavy chain and a light chain (beta-2 microglobulin). The heavy chain is anchored in the membrane. Class I molecules play a central role in the immune system by presenting peptides derived from the endoplasmic reticulum lumen so that they can be recognized by cytotoxic T cells. They are expressed in nearly all cells. The heavy chain is approximately 45 kDa and its gene contains 8 exons. Exon 1 encodes the leader peptide, exons 2 and 3 encode the alpha1 and alpha2 domains, which both bind the peptide, exon 4 encodes the alpha3 domain, exon 5 encodes the transmembrane region, and exons 6 and 7 encode the cytoplasmic tail. Polymorphisms within exon 2 and exon 3 are responsible for the peptide binding specificity of each class one molecule. Typing for these polymorphisms is routinely done for bone marrow and kidney transplantation. More than 6000 HLA-A alleles have been described. The HLA system plays an important role in the occurrence and outcome of infectious diseases, including those caused by the malaria parasite, the human immunodeficiency virus (HIV), and the severe acute respiratory syndrome coronavirus (SARS-CoV). The structural spike and the nucleocapsid proteins of the novel coronavirus SARS-CoV-2, which causes coronavirus disease 2019 (COVID-19), are reported to contain multiple Class I epitopes with predicted HLA restrictions. Individual HLA genetic variation may help explain different immune responses to a virus across a population.[provided by RefSeq, Aug 2020]

HLA-A links:

POLR1HASP (HGNC:):

POLR1HASP links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002116.8. 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-A	NM_002116.8	MANE Select	c.502A>T	p.Lys168*	stop_gained	Exon 3 of 8	NP_002107.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
HLA-A	ENST00000376809.10	TSL:6 MANE Select	c.502A>T	p.Lys168*	stop_gained	Exon 3 of 8	ENSP00000366005.5
HLA-A	ENST00000952344.1		c.502A>T	p.Lys168*	stop_gained	Exon 3 of 8	ENSP00000622403.1
HLA-A	ENST00000706894.1		c.502A>T	p.Lys168*	stop_gained	Exon 4 of 8	ENSP00000516610.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

43264

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

692348

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

352284

African (AFR)

AF:

0.00

AC:

AN:

19102

American (AMR)

AF:

0.00

AC:

AN:

19966

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12542

East Asian (EAS)

AF:

0.00

AC:

AN:

15198

South Asian (SAS)

AF:

0.00

AC:

AN:

55016

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29270

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2436

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

509248

Other (OTH)

AF:

0.00

AC:

AN:

29570

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

43264

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

20964

African (AFR)

AF:

0.00

AC:

AN:

11308

American (AMR)

AF:

0.00

AC:

AN:

3062

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

846

East Asian (EAS)

AF:

0.00

AC:

AN:

798

South Asian (SAS)

AF:

0.00

AC:

AN:

816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4526

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

21020

Other (OTH)

AF:

0.00

AC:

AN:

506

Alfa

AF:

0.00

Hom.:

486

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.39

BayesDel_noAF

Pathogenic

0.33

CADD

Uncertain

(source)

DANN

Uncertain

0.98

Eigen

Benign

-0.69

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.13

PhyloP100

-0.51

Vest4

0.66

GERP RS

-1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=169/31

disease causing (fs/PTC)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over