rs775190999

Variant names:

• chr6-149888548-A-C
• rs775190999
• NM_001394057.1:c.742T>G

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.742T>G​(p.Trp248Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,828 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: RAET1E NM_001394057.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.74
• 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=0.14565495).

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.742T>G	p.Trp248Gly	missense	Exon 6 of 6	NP_001380986.1	Q8TD07-1
	RAET1E	NM_139165.3		c.742T>G	p.Trp248Gly	missense	Exon 4 of 4	NP_631904.1	Q8TD07-1
	RAET1E	NM_001394056.1		c.742T>G	p.Trp248Gly	missense	Exon 6 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.742T>G	p.Trp248Gly	missense	Exon 6 of 6	ENSP00000349709.4	Q8TD07-1
	RAET1E	ENST00000367363.3	TSL:1	c.634T>G	p.Trp212Gly	missense	Exon 4 of 4	ENSP00000356332.3	Q8TD07-2
	RAET1E	ENST00000532335.5	TSL:1	c.622+800T>G		intron	N/A	ENSP00000437067.1	Q8TD07-3

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151974 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000358 AC: 9 AN: 251430 AF XY: 0.0000294

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000490

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461854 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 727232

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.000151 AC: 6 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111998

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151974 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 74234

African (AFR) AF: 0.00 AC: 0 AN: 41374

American (AMR) AF: 0.00 AC: 0 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67986

Other (OTH) AF: 0.00 AC: 0 AN: 2080

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000412 AC: 5

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.10
DANN	Benign	0.45
DEOGEN2	Benign	0.015	T
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.0057	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.91	T
PhyloP100		-1.7
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.51	N
REVEL	Benign	0.10
Sift	Benign	0.051	T
Sift4G	Benign	0.36	T
Polyphen		0.0	B
Vest4		0.15
MutPred		0.73		Loss of stability (P = 0.1213)
MVP		0.085
MPC		0.13
ClinPred		0.059	T
GERP RS		-4.9
Varity_R		0.13
gMVP		0.42
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs775190999; hg19: chr6-150209684;