6-149889999-C-T

Variant names:

• chr6-149889999-C-T
• NM_001394057.1:c.232G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001394057.1(RAET1E):​c.232G>A​(p.Gly78Arg) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RAET1E NM_001394057.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.100

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34765697).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAET1E	NM_001394057.1	c.232G>A	p.Gly78Arg	missense_variant	Exon 4 of 6	ENST00000357183.9	NP_001380986.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAET1E	ENST00000357183.9	c.232G>A	p.Gly78Arg	missense_variant	Exon 4 of 6	1	NM_001394057.1	ENSP00000349709.4
ENSG00000285991	ENST00000647612.1	n.232G>A		non_coding_transcript_exon_variant	Exon 3 of 15			ENSP00000498179.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 04, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.232G>A (p.G78R) alteration is located in exon 1 (coding exon 1) of the RAET1E gene. This alteration results from a G to A substitution at nucleotide position 232, causing the glycine (G) at amino acid position 78 to be replaced by an arginine (R). 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	Pathogenic	0.64
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	.;T;.;.;.
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.030	N
LIST_S2	Uncertain	0.86	D;D;D;D;T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.35	T;T;T;T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.29	T
PROVEAN	Pathogenic	-7.0	D;D;D;D;D
REVEL	Benign	0.097
Sift	Uncertain	0.0020	D;D;D;D;D
Sift4G	Uncertain	0.010	D;D;D;D;.
Polyphen		1.0	D;D;D;.;.
Vest4		0.35
MutPred		0.66		Gain of methylation at G78 (P = 0.0329);Gain of methylation at G78 (P = 0.0329);.;Gain of methylation at G78 (P = 0.0329);Gain of methylation at G78 (P = 0.0329);
MVP		0.31
MPC		0.45
ClinPred		0.64	D
GERP RS		2.0
Varity_R		0.61
gMVP		0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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: chr6-150211135;