6-31269346-G-C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_002117.6(HLA-C):c.1088C>G(p.Thr363Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/20 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 0.000060 ( 1 hom., cov: 7)

Exomes 𝑓: 0.000014 ( 2 hom. )

Failed GnomAD Quality Control

Consequence

HLA-C
NM_002117.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.13

Publications

0 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:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_002117.6, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09309575).

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.1088C>G	p.Thr363Ser	missense	Exon 7 of 8	NP_002108.4	P10321-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HLA-C	ENST00000376228.10	TSL:6 MANE Select	c.1088C>G	p.Thr363Ser	missense	Exon 7 of 8	ENSP00000365402.5	P10321-1
HLA-C	ENST00000383329.7	TSL:6	c.1106C>G	p.Thr369Ser	missense	Exon 7 of 8	ENSP00000372819.3	A2AEA2
HLA-C	ENST00000956155.1		c.1088C>G	p.Thr363Ser	missense	Exon 7 of 8	ENSP00000626214.1

Frequencies

GnomAD3 genomes

AF:

0.0000596

AC:

AN:

67136

Hom.:

Cov.:

show subpopulations

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:

0.000110

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000401

AC:

AN:

249122

AF XY:

0.00000741

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:

0.00000890

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000144

AC:

AN:

832142

Hom.:

Cov.:

AF XY:

0.00000968

AC XY:

AN XY:

413242

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

15342

American (AMR)

AF:

0.00

AC:

AN:

22572

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9470

East Asian (EAS)

AF:

0.00

AC:

AN:

18522

South Asian (SAS)

AF:

0.00

AC:

AN:

44664

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30072

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2386

European-Non Finnish (NFE)

AF:

0.0000168

AC:

AN:

655456

Other (OTH)

AF:

0.0000297

AC:

AN:

33658

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.644

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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: AS_VQSR

AF:

0.0000596

AC:

AN:

67136

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

31964

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

13508

American (AMR)

AF:

0.00

AC:

AN:

6096

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

938

East Asian (EAS)

AF:

0.00

AC:

AN:

1858

South Asian (SAS)

AF:

0.00

AC:

AN:

1796

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4998

Middle Eastern (MID)

AF:

0.00

AC:

AN:

144

European-Non Finnish (NFE)

AF:

0.000110

AC:

AN:

36454

Other (OTH)

AF:

0.00

AC:

AN:

820

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.825

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

1.7

(source)

DANN

Benign

0.24

DEOGEN2

Benign

0.0013

Eigen

Benign

-0.95

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.055

LIST_S2

Benign

0.61

M_CAP

Benign

0.0016

MetaRNN

Benign

0.093

MetaSVM

Benign

-0.94

PhyloP100

-1.1

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.19

REVEL

Benign

0.087

Sift

Uncertain

0.0020

Sift4G

Benign

0.45

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.055

Mutation Taster

=100/0

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over