6-149888647-C-G

Position:

• chr6-149888647-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 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. 14/22 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: 25)
• Consequence: RAET1E NM_001394057.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.687

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:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAET1E	NM_001394057.1	c.643G>C	p.Asp215His	missense_variant	6/6	ENST00000357183.9	NP_001380986.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAET1E	ENST00000357183.9	c.643G>C	p.Asp215His	missense_variant	6/6	1	NM_001394057.1	ENSP00000349709.4
ENSG00000285991	ENST00000647612.1	n.643G>C		non_coding_transcript_exon_variant	5/15			ENSP00000498179.1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 25

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 16, 2024

The c.643G>C (p.D215H) alteration is located in exon 1 (coding exon 1) of the RAET1E gene. This alteration results from a G to C substitution at nucleotide position 643, causing the aspartic acid (D) at amino acid position 215 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.089	T;T
MetaSVM	Benign	-0.93	T
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.045
Sift	Benign	0.060	T;T
Sift4G	Benign	0.098	T;D
Polyphen		0.84	P;D
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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-150209783;