6-149888647-C-G

Variant names:

• chr6-149888647-C-G
• NM_001394057.1:c.643G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001394057.1(RAET1E):​c.643G>C​(p.Asp215His) 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. 15/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D215G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 25)
• Consequence: RAET1E NM_001394057.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.687
• Publications: 0 publications found

Genes affected

RAET1E (HGNC:16793): (retinoic acid early transcript 1E) This gene belong to the RAET1 family, which consists of major histocompatibility complex (MHC) class I-related genes located in a cluster on chromosome 6q24.2-q25.3. This and RAET1G protein differ from other RAET1 proteins in that they have type I membrane-spanning sequences at their C termini rather than glycosylphosphatidylinositol anchor sequences. This protein functions as a ligand for NKG2D receptor, which is expressed on the surface of several types of immune cells, and is involved in innate and adaptive immune responses. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Aug 2011]

ENSG00000285991 (HGNC:):

RAET1E-AS1 (HGNC:48994): (RAET1E antisense RNA 1)

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.088859856).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394057.1. 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
	RAET1E	NM_001394057.1	MANE Select	c.643G>C	p.Asp215His	missense	Exon 6 of 6	NP_001380986.1	Q8TD07-1
	RAET1E	NM_139165.3		c.643G>C	p.Asp215His	missense	Exon 4 of 4	NP_631904.1	Q8TD07-1
	RAET1E	NM_001394056.1		c.643G>C	p.Asp215His	missense	Exon 6 of 7	NP_001380985.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAET1E	ENST00000357183.9	TSL:1 MANE Select	c.643G>C	p.Asp215His	missense	Exon 6 of 6	ENSP00000349709.4	Q8TD07-1
	RAET1E	ENST00000367363.3	TSL:1	c.535G>C	p.Asp179His	missense	Exon 4 of 4	ENSP00000356332.3	Q8TD07-2
	RAET1E	ENST00000532335.5	TSL:1	c.622+701G>C		intron	N/A	ENSP00000437067.1	Q8TD07-3

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 25

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.2
DANN	Benign	0.86
DEOGEN2	Benign	0.012	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-0.93	T
PhyloP100		-0.69
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.045
Sift	Benign	0.060	T
Sift4G	Benign	0.098	T
Polyphen		0.84	P
Vest4		0.064
MutPred		0.34		Loss of sheet (P = 0.0817)
MVP		0.17
MPC		0.086
ClinPred		0.20	T
GERP RS		-1.2
Varity_R		0.051
gMVP		0.11
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.20		Position offset: 20

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr6-150209783;