Variant 6-149919676-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000367360.7(RAET1G):c.226C>A(p.Pro76Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,670 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

RAET1G
ENST00000367360.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.762

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:

RAET1G (HGNC:):

RAET1G links:

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ACMG classification

Classification made for transcript

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=0.35270935).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAET1G	NM_001001788.4 linkuse as main transcript	c.226C>A	p.Pro76Thr	missense_variant	2/5	ENST00000367360.7	NP_001001788.2	Q6H3X3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RAET1G	ENST00000367360.7 linkuse as main transcript	c.226C>A	p.Pro76Thr	missense_variant	2/5	1	NM_001001788.4	ENSP00000356329.2	Q6H3X3-1
RAET1G	ENST00000479265.1 linkuse as main transcript	c.226C>A	p.Pro76Thr	missense_variant	2/3	2		ENSP00000417503.1	C9JAK3
RAET1G	ENST00000367361.6 linkuse as main transcript	n.226C>A		non_coding_transcript_exon_variant	2/5	2		ENSP00000356330.2	Q6H3X3-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461670

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727144

show subpopulations

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.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 04, 2024

The c.226C>A (p.P76T) alteration is located in exon 2 (coding exon 2) of the RAET1G gene. This alteration results from a C to A substitution at nucleotide position 226, causing the proline (P) at amino acid position 76 to be replaced by a threonine (T). 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

0.088

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.59

DANN

Benign

0.93

DEOGEN2

Benign

0.017

T;T

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.31

T;T

M_CAP

Benign

0.00091

MetaRNN

Benign

0.35

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.26

PROVEAN

Uncertain

-3.6

D;D

REVEL

Benign

0.061

Sift

Benign

0.42

T;T

Sift4G

Benign

0.11

T;T

Polyphen

0.98

D;.

Vest4

0.034

MutPred

0.73

Gain of MoRF binding (P = 0.0593);Gain of MoRF binding (P = 0.0593);

MVP

0.29

MPC

0.27

ClinPred

0.31

GERP RS

0.20

Varity_R

0.14

gMVP

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over