6-149889984-C-T

Variant names:

• chr6-149889984-C-T
• rs1269331583
• NM_001394057.1:c.247G>A

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.247G>A​(p.Ala83Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A83V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RAET1E NM_001394057.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.910
• 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=0.07512346).

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.247G>A	p.Ala83Thr	missense	Exon 4 of 6	NP_001380986.1	Q8TD07-1
	RAET1E	NM_139165.3		c.247G>A	p.Ala83Thr	missense	Exon 2 of 4	NP_631904.1	Q8TD07-1
	RAET1E	NM_001394056.1		c.247G>A	p.Ala83Thr	missense	Exon 4 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.247G>A	p.Ala83Thr	missense	Exon 4 of 6	ENSP00000349709.4	Q8TD07-1
	RAET1E	ENST00000367363.3	TSL:1	c.139G>A	p.Ala47Thr	missense	Exon 2 of 4	ENSP00000356332.3	Q8TD07-2
	RAET1E	ENST00000532335.5	TSL:1	c.247G>A	p.Ala83Thr	missense	Exon 3 of 5	ENSP00000437067.1	Q8TD07-3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461862 Hom.: 0 Cov.: 40 AF XY: 0.00000275 AC XY: 2 AN XY: 727236

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111982

Other (OTH) AF: 0.00 AC: 0 AN: 60394

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000770867), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.1
DANN	Benign	0.95
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0047	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.91
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.98	N
REVEL	Benign	0.097
Sift	Benign	0.61	T
Sift4G	Benign	0.51	T
Polyphen		0.67	P
Vest4		0.052
MutPred		0.52		Gain of methylation at K79 (P = 0.0617)
MVP		0.17
MPC		0.24
ClinPred		0.33	T
GERP RS		-4.3
Varity_R		0.070
gMVP		0.12
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1269331583; hg19: chr6-150211120;