Genetic Variant NM_001001788.4:c.76G>C (chr6-149922935-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_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. 15/21 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

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

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

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.76G>C	p.Gly26Arg	missense	Exon 1 of 5	NP_001001788.2	Q6H3X3-1
	RAET1G	NR_130110.2		n.187G>C		non_coding_transcript_exon	Exon 1 of 5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RAET1G	ENST00000367360.7	TSL:1 MANE Select	c.76G>C	p.Gly26Arg	missense	Exon 1 of 5	ENSP00000356329.2	Q6H3X3-1
RAET1G	ENST00000962108.1		c.76G>C	p.Gly26Arg	missense	Exon 1 of 5	ENSP00000632167.1
RAET1G	ENST00000479265.1	TSL:2	c.76G>C	p.Gly26Arg	missense	Exon 1 of 3	ENSP00000417503.1	C9JAK3

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

GnomAD2 exomes

AF:

0.0000185

AC:

AN:

215824

AF XY:

0.0000172

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 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

African (AFR)

AF:

0.000300

AC:

AN:

33314

American (AMR)

AF:

0.0000485

AC:

AN:

41270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25550

East Asian (EAS)

AF:

0.0000770

AC:

AN:

38970

South Asian (SAS)

AF:

0.00

AC:

AN:

82578

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51646

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

9.06e-7

AC:

AN:

1103414

Other (OTH)

AF:

0.0000502

AC:

AN:

59732

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000184

AC:

AN:

152376

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74514

show subpopulations

African (AFR)

AF:

0.000577

AC:

AN:

41586

American (AMR)

AF:

0.000131

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68040

Other (OTH)

AF:

0.000945

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000121

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.61

CADD

Benign

9.0

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.015

Eigen

Benign

-0.91

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.056

LIST_S2

Benign

0.50

M_CAP

Benign

0.0013

MetaRNN

Benign

0.075

MetaSVM

Benign

-0.95

PhyloP100

-0.12

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.4

REVEL

Benign

0.056

Sift

Benign

0.046

Sift4G

Benign

0.10

Polyphen

0.24

Vest4

0.23

MutPred

0.53

Gain of solvent accessibility (P = 0.0171)

MVP

0.24

MPC

0.25

ClinPred

0.031

GERP RS

0.43

PromoterAI

0.042

Neutral

(source)

Varity_R

0.082

gMVP

0.22

Mutation Taster

=96/4

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over