6-149889971-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001394057.1(RAET1E):​c.260G>T​(p.Trp87Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

RAET1E
NM_001394057.1 missense

Scores

2
3
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0650
Variant links:
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]
RAET1E-AS1 (HGNC:48994): (RAET1E antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.906

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RAET1ENM_001394057.1 linkuse as main transcriptc.260G>T p.Trp87Leu missense_variant 4/6 ENST00000357183.9
RAET1E-LRP11NR_182438.1 linkuse as main transcriptn.678G>T non_coding_transcript_exon_variant 3/15
RAET1E-AS1NR_045126.1 linkuse as main transcriptn.885+25589C>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RAET1EENST00000357183.9 linkuse as main transcriptc.260G>T p.Trp87Leu missense_variant 4/61 NM_001394057.1 P2Q8TD07-1
RAET1E-AS1ENST00000605899.1 linkuse as main transcriptn.114+4298C>A intron_variant, non_coding_transcript_variant 5
RAET1E-AS1ENST00000606915.1 linkuse as main transcriptn.889+25589C>A intron_variant, non_coding_transcript_variant 1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251486
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135918
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000109
AC:
16
AN:
1461880
Hom.:
0
Cov.:
41
AF XY:
0.00000963
AC XY:
7
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000135
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31
Bravo
AF:
0.00000756
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 17, 2023The c.260G>T (p.W87L) alteration is located in exon 1 (coding exon 1) of the RAET1E gene. This alteration results from a G to T substitution at nucleotide position 260, causing the tryptophan (W) at amino acid position 87 to be replaced by a leucine (L). 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
Uncertain
0.42
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
15
DANN
Benign
0.93
DEOGEN2
Benign
0.12
.;T;.;.
Eigen
Benign
-0.55
Eigen_PC
Benign
-0.78
FATHMM_MKL
Benign
0.029
N
LIST_S2
Benign
0.59
T;T;T;T
M_CAP
Benign
0.0016
T
MetaRNN
Pathogenic
0.91
D;D;D;D
MetaSVM
Benign
-1.1
T
MutationTaster
Benign
1.0
N;N;N;N
PrimateAI
Benign
0.31
T
PROVEAN
Pathogenic
-12
D;D;D;D
REVEL
Benign
0.075
Sift
Uncertain
0.0010
D;D;D;D
Sift4G
Uncertain
0.013
D;D;D;D
Polyphen
0.53
P;P;P;.
Vest4
0.36
MutPred
0.85
Gain of disorder (P = 0.0575);Gain of disorder (P = 0.0575);.;Gain of disorder (P = 0.0575);
MVP
0.21
MPC
0.18
ClinPred
0.90
D
GERP RS
0.89
Varity_R
0.34
gMVP
0.63

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs758548853; hg19: chr6-150211107; API