6-149922935-C-G

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001001788.4(RAET1G):c.76G>C(p.Gly26Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000295 in 1,594,588 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

RAET1G
NM_001001788.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.121

Variant links:

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]

RAET1G links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07544494).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAET1G	NM_001001788.4 link	c.76G>C	p.Gly26Arg	missense_variant	Exon 1 of 5	ENST00000367360.7	NP_001001788.2	Q6H3X3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RAET1G	ENST00000367360.7 link	c.76G>C	p.Gly26Arg	missense_variant	Exon 1 of 5	1	NM_001001788.4	ENSP00000356329.2	Q6H3X3-1
RAET1G	ENST00000479265.1 link	c.76G>C	p.Gly26Arg	missense_variant	Exon 1 of 3	2		ENSP00000417503.1	C9JAK3
RAET1G	ENST00000367361.6 link	n.76G>C		non_coding_transcript_exon_variant	Exon 1 of 5	2		ENSP00000356330.2	Q6H3X3-2

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152258

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000506

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.0000185

AC:

AN:

215824

Hom.:

AF XY:

0.0000172

AC XY:

AN XY:

116406

show subpopulations

Gnomad AFR exome

AF:

0.000317

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000132

AC:

AN:

1442212

Hom.:

Cov.:

AF XY:

0.0000112

AC XY:

AN XY:

715388

show subpopulations

Gnomad4 AFR exome

AF:

0.000300

Gnomad4 AMR exome

AF:

0.0000485

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000770

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.06e-7

Gnomad4 OTH exome

AF:

0.0000502

GnomAD4 genome

AF:

0.000184

AC:

AN:

152376

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.000577

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000945

Bravo

AF:

0.000121

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 03, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.76G>C (p.G26R) alteration is located in exon 1 (coding exon 1) of the RAET1G gene. This alteration results from a G to C substitution at nucleotide position 76, causing the glycine (G) at amino acid position 26 to be replaced by an arginine (R). 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

0.19

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.61

CADD

Benign

9.0

DANN

Benign

0.88

DEOGEN2

Benign

0.015

T;T

Eigen

Benign

-0.91

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.056

LIST_S2

Benign

0.50

T;T

M_CAP

Benign

0.0013

MetaRNN

Benign

0.075

T;T

MetaSVM

Benign

-0.95

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.056

Sift

Benign

0.046

D;T

Sift4G

Benign

0.10

T;T

Polyphen

0.24

B;.

Vest4

0.23

MutPred

0.53

Gain of solvent accessibility (P = 0.0171);Gain of solvent accessibility (P = 0.0171);

MVP

0.24

MPC

0.25

ClinPred

0.031

GERP RS

0.43

Varity_R

0.082

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

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