6-149890868-G-A

Position:

chr6-149890868-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001394057.1(RAET1E):c.34C>T(p.Arg12Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,613,422 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R12H) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

RAET1E
NM_001394057.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -5.61

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 links:

RAET1E-LRP11 (HGNC:):

RAET1E-LRP11 links:

RAET1E-AS1 (HGNC:48994): (RAET1E antisense RNA 1)

RAET1E-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.049320877).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RAET1E	NM_001394057.1 linkuse as main transcript	c.34C>T	p.Arg12Cys	missense_variant	3/6	ENST00000357183.9	NP_001380986.1
RAET1E-LRP11	NR_182438.1 linkuse as main transcript	n.452C>T		non_coding_transcript_exon_variant	2/15
RAET1E-AS1	NR_045126.1 linkuse as main transcript	n.885+26486G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAET1E	ENST00000357183.9 linkuse as main transcript	c.34C>T	p.Arg12Cys	missense_variant	3/6	1	NM_001394057.1	ENSP00000349709	P2	Q8TD07-1
RAET1E-AS1	ENST00000605899.1 linkuse as main transcript	n.114+5195G>A		intron_variant, non_coding_transcript_variant		5
RAET1E-AS1	ENST00000606915.1 linkuse as main transcript	n.889+26486G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251374

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135852

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

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:

0.0000287

AC:

AN:

1461146

Hom.:

Cov.:

AF XY:

0.0000330

AC XY:

AN XY:

726964

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000928

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000243

Gnomad4 OTH exome

AF:

0.0000994

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152276

Hom.:

Cov.:

AF XY:

0.0000940

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000946

Bravo

AF:

0.0000680

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.0000545

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 submitter

clinical testing

Ambry Genetics

Jan 03, 2024

The c.34C>T (p.R12C) alteration is located in exon 1 (coding exon 1) of the RAET1E gene. This alteration results from a C to T substitution at nucleotide position 34, causing the arginine (R) at amino acid position 12 to be replaced by a cysteine (C). 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

Benign

0.11

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.57

CADD

Benign

0.0060

DANN

Benign

0.80

DEOGEN2

Benign

0.015

.;T;.;.;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0022

LIST_S2

Benign

0.48

T;T;T;T;T

M_CAP

Benign

0.0011

MetaRNN

Benign

0.049

T;T;T;T;T

MetaSVM

Benign

-0.98

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.47

N;N;N;N;N

REVEL

Benign

0.021

Sift

Benign

0.060

T;T;T;T;T

Sift4G

Uncertain

0.049

D;T;D;T;.

Polyphen

0.0020

B;B;B;.;.

Vest4

0.073

MutPred

0.37

Loss of MoRF binding (P = 0.0077);Loss of MoRF binding (P = 0.0077);Loss of MoRF binding (P = 0.0077);Loss of MoRF binding (P = 0.0077);Loss of MoRF binding (P = 0.0077);

MVP

0.072

MPC

0.096

ClinPred

0.048

GERP RS

-4.4

Varity_R

0.046

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over