6-149919240-C-T

Variant names:

• chr6-149919240-C-T
• NM_001001788.4:c.434G>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001001788.4(RAET1G):​c.434G>A​(p.Gly145Glu) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RAET1G NM_001001788.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.117
• Publications: 0 publications found

Genes affected

RAET1G (HGNC:16795): (retinoic acid early transcript 1G) This gene encodes a member of the major histocompatibility complex (MHC) class I family of proteins. Although the encoded protein includes C-terminal transmembrane and cytoplasmic domains, proteolytic processing results in the removal of these domains and subsequent tethering to the plasma membrane by a glycosylphosphatidylinositol (GPI)-anchor. The encoded protein is one of several related ligands of the natural killer group 2, member D (NKG2D) receptor, which functions as an activating receptor in innate and adaptive immunity. This gene is present in a gene cluster on chromosome 6. [provided by RefSeq, Jul 2015]

RAET1E-AS1 (HGNC:):

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.9

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001788.4. 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
	RAET1G	NM_001001788.4	MANE Select	c.434G>A	p.Gly145Glu	missense	Exon 3 of 5	NP_001001788.2	Q6H3X3-1
	RAET1E-AS1	NR_045126.1		n.939C>T		non_coding_transcript_exon	Exon 2 of 2
	RAET1E-AS1	NR_045127.1		n.223C>T		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAET1G	ENST00000367360.7	TSL:1 MANE Select	c.434G>A	p.Gly145Glu	missense	Exon 3 of 5	ENSP00000356329.2	Q6H3X3-1
	RAET1E-AS1	ENST00000606915.2	TSL:1	n.943C>T		non_coding_transcript_exon	Exon 2 of 2
	RAET1G	ENST00000479265.1	TSL:2	c.434G>A	p.Gly145Glu	missense	Exon 3 of 3	ENSP00000417503.1	C9JAK3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

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	Uncertain	0.41
BayesDel_addAF	Benign	-0.0036	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.014	N
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.0013	T
MetaRNN	Pathogenic	0.90	D
MetaSVM	Benign	-1.0	T
PhyloP100		0.12
PrimateAI	Benign	0.28	T
PROVEAN	Pathogenic	-7.5	D
REVEL	Benign	0.20
Sift	Benign	0.033	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.47
MutPred		0.95		Loss of catalytic residue at I147 (P = 0.0956)
MVP		0.27
MPC		0.86
ClinPred		0.94	D
GERP RS		1.5
Varity_R		0.40
gMVP		0.42
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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

hg19: chr6-150240376;