6-30490287-G-C

Variant names:

• chr6-30490287-G-C
• rs1264457
• NM_005516.6:c.382G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005516.6(HLA-E):​c.382G>C​(p.Gly128Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 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: not found (cov: 32)
• Consequence: HLA-E NM_005516.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02
• Publications: 0 publications found

Genes affected

HLA-E (HGNC:4962): (major histocompatibility complex, class I, E) HLA-E 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. HLA-E binds a restricted subset of peptides derived from the leader peptides of other class I molecules. 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 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. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28518444).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005516.6. 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-E	NM_005516.6	MANE Select	c.382G>C	p.Gly128Arg	missense	Exon 3 of 8	NP_005507.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-E	ENST00000376630.5	TSL:6 MANE Select	c.382G>C	p.Gly128Arg	missense	Exon 3 of 8	ENSP00000365817.4	P13747
	HLA-E	ENST00000896643.1		c.382G>C	p.Gly128Arg	missense	Exon 3 of 8	ENSP00000566702.1
	HLA-E	ENST00000896637.1		c.382G>C	p.Gly128Arg	missense	Exon 3 of 8	ENSP00000566696.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 54

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	20
DANN	Benign	0.97
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.019	N
M_CAP	Benign	0.078	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-1.2	T
PhyloP100		1.0
PrimateAI	Benign	0.31	T
PROVEAN	Pathogenic	-6.3	D
REVEL	Benign	0.051
Sift	Benign	0.051	T
Sift4G	Uncertain	0.058	T
Vest4		0.21
MutPred		0.73		Loss of methylation at R129 (P = 0.0423)
MVP		0.072
MPC		0.93
ClinPred		0.35	T
GERP RS		0.76
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Varity_R		0.24
gMVP		0.82
Mutation Taster		=67/33	polymorphism

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

Other links and lift over

dbSNP: rs1264457; hg19: chr6-30458064;