6-150020182-A-G

Position:

• chr6-150020182-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_130900.3(RAET1L):​c.689T>C​(p.Ile230Thr) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 21)
• Consequence: RAET1L NM_130900.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -5.98

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]

ACMG classification

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=0.16422516).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAET1L	NM_130900.3	c.689T>C	p.Ile230Thr	missense_variant	4/5	ENST00000367341.6	NP_570970.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAET1L	ENST00000367341.6	c.689T>C	p.Ile230Thr	missense_variant	4/5	1	NM_130900.3	ENSP00000356310.1
RAET1L	ENST00000286380.2	c.689T>C	p.Ile230Thr	missense_variant	4/4	1		ENSP00000286380.2

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome Cov.: 17

GnomAD4 genome Cov.: 21

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 19, 2024

The c.689T>C (p.I230T) alteration is located in exon 4 (coding exon 4) of the RAET1L gene. This alteration results from a T to C substitution at nucleotide position 689, causing the isoleucine (I) at amino acid position 230 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	0.24
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.029
DANN	Benign	0.16
DEOGEN2	Benign	0.0043	T;T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0013	N
LIST_S2	Benign	0.40	.;T
M_CAP	Benign	0.00089	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-0.95	T
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.17	N;N
REVEL	Benign	0.027
Sift	Benign	0.43	T;T
Sift4G	Benign	0.19	T;T
Polyphen		0.11	B;B
Vest4		0.20
MutPred		0.63		Loss of helix (P = 0.0068);Loss of helix (P = 0.0068);
MVP		0.030
MPC		0.14
ClinPred		0.031	T
GERP RS		-3.9
Varity_R		0.033
gMVP		0.066

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-150341318;