6-150021094-A-G

Position:

• chr6-150021094-A-G

Variant summary

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

The NM_130900.3(RAET1L):​c.442T>C​(p.Phe148Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RAET1L NM_130900.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.732

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAET1L	NM_130900.3	c.442T>C	p.Phe148Leu	missense_variant	3/5	ENST00000367341.6	NP_570970.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAET1L	ENST00000367341.6	c.442T>C	p.Phe148Leu	missense_variant	3/5	1	NM_130900.3	ENSP00000356310.1
RAET1L	ENST00000286380.2	c.442T>C	p.Phe148Leu	missense_variant	3/4	1		ENSP00000286380.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 91

GnomAD4 genome Cov.: 32

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

Jun 19, 2024

The c.442T>C (p.F148L) alteration is located in exon 3 (coding exon 3) of the RAET1L gene. This alteration results from a T to C substitution at nucleotide position 442, causing the phenylalanine (F) at amino acid position 148 to be replaced by a leucine (L). 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	Pathogenic	0.93
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	13
DANN	Benign	0.87
DEOGEN2	Benign	0.0033	T;T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.044	N
LIST_S2	Uncertain	0.91	.;D
M_CAP	Benign	0.0012	T
MetaRNN	Uncertain	0.48	T;T
MetaSVM	Benign	-0.99	T
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-2.5	D;D
REVEL	Benign	0.11
Sift	Benign	0.095	T;T
Sift4G	Benign	0.10	T;T
Polyphen		0.80	P;P
Vest4		0.26
MutPred		0.70		Gain of MoRF binding (P = 0.2303);Gain of MoRF binding (P = 0.2303);
MVP		0.048
MPC		0.17
ClinPred		0.48	T
GERP RS		-3.7
Varity_R		0.32
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-150342230;