Variant 6-150022045-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_130900.3(RAET1L):c.284G>C(p.Arg95Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000713 in 1,402,514 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000073 ( 0 hom., cov: 20)

Exomes 𝑓: 0.0000071 ( 0 hom. )

Consequence

RAET1L
NM_130900.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.94

Variant links:

Genes affected

RAET1L (HGNC:16798): (retinoic acid early transcript 1L) RAET1L belongs to the RAET1 family of major histocompatibility complex (MHC) class I-related genes, which are located within a 180-kb cluster on chromosome 6q24.2-q25.3. The REAT1 genes encode glycoproteins that contain extracellular alpha-1 and alpha-2 domains, but they lack the membrane proximal Ig-like alpha-3 domain. Most RAET1 glycoproteins are anchored to the membrane via glycosylphosphatidylinositol (GPI) linkage (Radosavljevic et al., 2002 [PubMed 11827464]).[supplied by OMIM, Mar 2008]

RAET1L links:

Genome browser will be placed here

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=0.37718785).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAET1L	NM_130900.3 linkuse as main transcript	c.284G>C	p.Arg95Thr	missense_variant	2/5	ENST00000367341.6	NP_570970.2	Q5VY80

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAET1L	ENST00000367341.6 linkuse as main transcript	c.284G>C	p.Arg95Thr	missense_variant	2/5	1	NM_130900.3	ENSP00000356310.1		Q5VY80
RAET1L	ENST00000286380.2 linkuse as main transcript	c.284G>C	p.Arg95Thr	missense_variant	2/4	1		ENSP00000286380.2		Q5VY80

Frequencies

GnomAD3 genomes

AF:

0.00000732

AC:

AN:

136646

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000165

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000912

AC:

AN:

219276

Hom.:

AF XY:

0.00000849

AC XY:

AN XY:

117854

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000298

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000369

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000711

AC:

AN:

1265868

Hom.:

Cov.:

AF XY:

0.00000473

AC XY:

AN XY:

633614

show subpopulations

Gnomad4 AFR exome

AF:

0.0000313

Gnomad4 AMR exome

AF:

0.0000229

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000124

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000535

Gnomad4 OTH exome

AF:

0.0000183

GnomAD4 genome

AF:

0.00000732

AC:

AN:

136646

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

66240

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000165

Gnomad4 OTH

AF:

0.00

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

Dec 04, 2024

The c.284G>C (p.R95T) alteration is located in exon 2 (coding exon 2) of the RAET1L gene. This alteration results from a G to C substitution at nucleotide position 284, causing the arginine (R) at amino acid position 95 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

0.15

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.67

CADD

Benign

2.9

DANN

Benign

0.93

DEOGEN2

Benign

0.0059

T;T

Eigen

Benign

-0.82

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0032

LIST_S2

Uncertain

0.89

.;D

M_CAP

Benign

0.0018

MetaRNN

Benign

0.38

T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.25

PROVEAN

Pathogenic

-4.9

D;D

REVEL

Benign

0.073

Sift

Benign

0.065

T;T

Sift4G

Uncertain

0.0090

D;D

Polyphen

0.98

D;D

Vest4

0.32

MutPred

0.65

Loss of MoRF binding (P = 0.0469);Loss of MoRF binding (P = 0.0469);

MVP

0.19

MPC

0.51

ClinPred

0.71

GERP RS

-3.2

Varity_R

0.17

gMVP

0.12

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