chr6-149919601-G-A

Position:

• chr6-149919601-G-A

Variant summary

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

The NM_001001788.4(RAET1G):​c.301C>T​(p.Leu101Phe) 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 NM_001001788.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.430

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]

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=0.17680806).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAET1G	NM_001001788.4	c.301C>T	p.Leu101Phe	missense_variant	2/5	ENST00000367360.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAET1G	ENST00000367360.7	c.301C>T	p.Leu101Phe	missense_variant	2/5	1	NM_001001788.4	P2
RAET1G	ENST00000479265.1	c.301C>T	p.Leu101Phe	missense_variant	2/3	2		A2
RAET1G	ENST00000367361.6	c.301C>T	p.Leu101Phe	missense_variant, NMD_transcript_variant	2/5	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461670 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727146

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.: 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

Jan 19, 2024

The c.301C>T (p.L101F) alteration is located in exon 2 (coding exon 2) of the RAET1G gene. This alteration results from a C to T substitution at nucleotide position 301, causing the leucine (L) at amino acid position 101 to be replaced by a phenylalanine (F). 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	0.25
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	13
DANN	Benign	0.96
DEOGEN2	Benign	0.058	T;T
Eigen	Benign	-0.89
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0047	N
LIST_S2	Benign	0.72	T;T
M_CAP	Benign	0.0010	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.6	D;D
REVEL	Benign	0.090
Sift	Benign	0.073	T;D
Sift4G	Benign	0.064	T;T
Polyphen		1.0	D;.
Vest4		0.061
MutPred		0.60		Loss of catalytic residue at T102 (P = 0.3136);Loss of catalytic residue at T102 (P = 0.3136);
MVP		0.061
MPC		0.21
ClinPred		0.84	D
GERP RS		-1.9
Varity_R		0.24
gMVP		0.16

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: chr6-150240737;