NM_002117.6:c.89G>T

Variant names:

Variant summary

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

The NM_002117.6(HLA-C):c.89G>T(p.Arg30Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 12)

Exomes 𝑓: 0.0000017 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HLA-C
NM_002117.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.481

Publications

13 publications found

Variant links:

Genes affected

HLA-C (HGNC:4933): (major histocompatibility complex, class I, C) HLA-C 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 endoplasmic reticulum lumen. They are expressed in nearly all cells. The heavy chain is approximately 45 kDa and its gene contains 8 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the alpha1 and alpha2 domain, 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. About 6000 HLA-C 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-C links:

ENSG00000288813 (HGNC:):

ENSG00000288813 links:

Genome browser will be placed here

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_002117.6. 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-C	NM_002117.6	MANE Select	c.89G>T	p.Arg30Met	missense	Exon 2 of 8	NP_002108.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
HLA-C	ENST00000376228.10	TSL:6 MANE Select	c.89G>T	p.Arg30Met	missense	Exon 2 of 8	ENSP00000365402.5
HLA-C	ENST00000383329.7	TSL:6	c.89G>T	p.Arg30Met	missense	Exon 2 of 8	ENSP00000372819.3
HLA-C	ENST00000956155.1		c.89G>T	p.Arg30Met	missense	Exon 2 of 8	ENSP00000626214.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

86092

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

GnomAD2 exomes

AF:

0.00000843

AC:

AN:

237132

AF XY:

0.0000154

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000168

AC:

AN:

1190084

Hom.:

Cov.:

AF XY:

0.00000168

AC XY:

AN XY:

594534

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

24582

American (AMR)

AF:

0.00

AC:

AN:

36034

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20748

East Asian (EAS)

AF:

0.0000366

AC:

AN:

27294

South Asian (SAS)

AF:

0.0000129

AC:

AN:

77280

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37570

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3774

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

914568

Other (OTH)

AF:

0.00

AC:

AN:

48234

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

86092

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

41232

African (AFR)

AF:

0.00

AC:

AN:

20688

American (AMR)

AF:

0.00

AC:

AN:

7516

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1648

East Asian (EAS)

AF:

0.00

AC:

AN:

2018

South Asian (SAS)

AF:

0.00

AC:

AN:

2500

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

188

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

44196

Other (OTH)

AF:

0.00

AC:

AN:

1058

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Benign

0.82

DEOGEN2

Benign

0.071

Eigen

Benign

-0.076

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.27

M_CAP

Benign

0.0035

MetaRNN

Uncertain

0.65

MetaSVM

Benign

-1.0

PhyloP100

0.48

PrimateAI

Benign

0.32

PROVEAN

Uncertain

-3.8

REVEL

Benign

0.11

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0020

Polyphen

0.83

Vest4

0.55

MutPred

0.72

Loss of methylation at R30 (P = 0.0343)

MVP

0.28

MPC

0.96

ClinPred

0.64

GERP RS

1.4

PromoterAI

0.056

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

gMVP

0.47

Mutation Taster

=98/2

polymorphism

(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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over