6-149889432-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001394057.1(RAET1E):c.538T>A(p.Tyr180Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RAET1E NM_001394057.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.211

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-LRP11 (HGNC:):

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

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2693052).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAET1E	NM_001394057.1	c.538T>A	p.Tyr180Asn	missense_variant	5/6	ENST00000357183.9
RAET1E-LRP11	NR_182438.1	n.956T>A		non_coding_transcript_exon_variant	4/15
RAET1E-AS1	NR_045126.1	n.885+25050A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAET1E	ENST00000357183.9	c.538T>A	p.Tyr180Asn	missense_variant	5/6	1	NM_001394057.1	P2
RAET1E-AS1	ENST00000605899.1	n.114+3759A>T		intron_variant, non_coding_transcript_variant		5
RAET1E-AS1	ENST00000606915.1	n.889+25050A>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 04, 2023

The c.538T>A (p.Y180N) alteration is located in exon 1 (coding exon 1) of the RAET1E gene. This alteration results from a T to A substitution at nucleotide position 538, causing the tyrosine (Y) at amino acid position 180 to be replaced by an asparagine (N). 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	0.30
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
Cadd	Benign	16
Dann	Benign	0.89
Eigen	Benign	-0.71
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.83	T;T;T;T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.27	T;T;T;T
MetaSVM	Benign	-0.70	T
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.38	T
PROVEAN	Pathogenic	-5.3	D;D;D;D
REVEL	Benign	0.090
Sift	Uncertain	0.017	D;D;D;D
Sift4G	Benign	0.15	T;D;D;T
Polyphen		0.99	D;D;D;.
Vest4		0.34
MutPred		0.49		Gain of disorder (P = 0.0188);Gain of disorder (P = 0.0188);.;Gain of disorder (P = 0.0188);
MVP		0.56
MPC		0.43
ClinPred		0.95	D
GERP RS		-7.6
Varity_R		0.37
gMVP		0.22

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

Other links and lift over

dbSNP: rs1777773566; hg19: chr6-150210568;