6-149889971-C-A
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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
NM_001394057.1 missense
Scores
2
3
13
Clinical Significance
Conservation
PhyloP100: -0.0650
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]
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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 |
---|---|---|---|---|---|---|---|
RAET1E | NM_001394057.1 | c.260G>T | p.Trp87Leu | missense_variant | 4/6 | ENST00000357183.9 | |
RAET1E-LRP11 | NR_182438.1 | n.678G>T | non_coding_transcript_exon_variant | 3/15 | |||
RAET1E-AS1 | NR_045126.1 | n.885+25589C>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RAET1E | ENST00000357183.9 | c.260G>T | p.Trp87Leu | missense_variant | 4/6 | 1 | NM_001394057.1 | P2 | |
RAET1E-AS1 | ENST00000605899.1 | n.114+4298C>A | intron_variant, non_coding_transcript_variant | 5 | |||||
RAET1E-AS1 | ENST00000606915.1 | n.889+25589C>A | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
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31
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251486Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135918
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GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461880Hom.: 0 Cov.: 41 AF XY: 0.00000963 AC XY: 7AN XY: 727242
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GnomAD4 genome Cov.: 31
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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 submitter | clinical testing | Ambry Genetics | Dec 17, 2023 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
.;T;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T;T
M_CAP
Benign
T
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N;N
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;D;D;D
REVEL
Benign
Sift
Uncertain
D;D;D;D
Sift4G
Uncertain
D;D;D;D
Polyphen
P;P;P;.
Vest4
MutPred
Gain of disorder (P = 0.0575);Gain of disorder (P = 0.0575);.;Gain of disorder (P = 0.0575);
MVP
MPC
0.18
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at