rs9383921

chr6-149889549-C-Gchr6-149889549-C-T

Variant summary

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

The NM_001394057.1(RAET1E):c.421G>C(p.Ala141Pro) 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. 12/20 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. A141T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RAET1E NM_001394057.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.880

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=0.3709064).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAET1E	NM_001394057.1	c.421G>C	p.Ala141Pro	missense_variant	5/6	ENST00000357183.9
RAET1E-LRP11	NR_182438.1	n.839G>C		non_coding_transcript_exon_variant	4/15
RAET1E-AS1	NR_045126.1	n.885+25167C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAET1E	ENST00000357183.9	c.421G>C	p.Ala141Pro	missense_variant	5/6	1	NM_001394057.1	P2
RAET1E-AS1	ENST00000605899.1	n.114+3876C>G		intron_variant, non_coding_transcript_variant		5
RAET1E-AS1	ENST00000606915.1	n.889+25167C>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.84e-7 AC: 1 AN: 1461864 Hom.: 0 Cov.: 46 AF XY: 0.00 AC XY: 0 AN XY: 727234

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
Cadd	Benign	8.3
Dann	Uncertain	0.99
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.60	T;T;T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.37	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-2.0	N;N;N;N
REVEL	Benign	0.069
Sift	Benign	0.042	D;D;D;D
Sift4G	Benign	0.11	T;T;T;T
Polyphen		0.92	P;P;P;.
Vest4		0.33
MutPred		0.45		Gain of methylation at K146 (P = 0.0976);Gain of methylation at K146 (P = 0.0976);.;Gain of methylation at K146 (P = 0.0976);
MVP		0.49
MPC		0.23
ClinPred		0.59	D
GERP RS		-2.1
Varity_R		0.28
gMVP		0.56

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: rs9383921; hg19: chr6-150210685;