6-149919610-C-T

Variant names:

• chr6-149919610-C-T
• rs1400031151
• NM_001001788.4:c.292G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001001788.4(RAET1G):​c.292G>A​(p.Val98Met) 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. 15/21 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. V98L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RAET1G NM_001001788.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.23
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10436651).

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.292G>A	p.Val98Met	missense	Exon 2 of 5	NP_001001788.2	Q6H3X3-1
	RAET1G	NR_130110.2		n.403G>A		non_coding_transcript_exon	Exon 2 of 5
	RAET1E-AS1	NR_045126.1		n.*102C>T		downstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAET1G	ENST00000367360.7	TSL:1 MANE Select	c.292G>A	p.Val98Met	missense	Exon 2 of 5	ENSP00000356329.2	Q6H3X3-1
	RAET1G	ENST00000962108.1		c.292G>A	p.Val98Met	missense	Exon 2 of 5	ENSP00000632167.1
	RAET1G	ENST00000479265.1	TSL:2	c.292G>A	p.Val98Met	missense	Exon 2 of 3	ENSP00000417503.1	C9JAK3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.23
DANN	Benign	0.94
DEOGEN2	Benign	0.0090	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0056	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.93	T
PhyloP100		-2.2
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.96	N
REVEL	Benign	0.037
Sift	Benign	0.26	T
Sift4G	Benign	0.24	T
Polyphen		0.24	B
Vest4		0.020
MutPred		0.60		Gain of catalytic residue at V98 (P = 0.2105)
MVP		0.10
MPC		0.37
ClinPred		0.24	T
GERP RS		0.36
Varity_R		0.055
gMVP		0.24
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1400031151; hg19: chr6-150240746;