Variant 12-49069053-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The ENST00000301068.11(RHEBL1):c.106G>C(p.Asp36His) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,684 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

RHEBL1
ENST00000301068.11 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.35

Variant links:

Genes affected

RHEBL1 (HGNC:21166): (RHEB like 1) Enables GTP binding activity. Involved in TOR signaling and positive regulation of NF-kappaB transcription factor activity. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

RHEBL1 links:

RHEBL1 (HGNC:):

RHEBL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.777

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHEBL1	NM_144593.3 linkuse as main transcript	c.106G>C	p.Asp36His	missense_variant	2/8	ENST00000301068.11	NP_653194.1	Q8TAI7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RHEBL1	ENST00000301068.11 linkuse as main transcript	c.106G>C	p.Asp36His	missense_variant	2/8	1	NM_144593.3	ENSP00000301068.6	Q8TAI7-1
RHEBL1	ENST00000420065.5 linkuse as main transcript	n.106G>C		non_coding_transcript_exon_variant	2/7	1		ENSP00000409818.1	C9JQQ1
RHEBL1	ENST00000550797.1 linkuse as main transcript	n.174G>C		non_coding_transcript_exon_variant	2/8	1		ENSP00000446726.1	Q8TAI7-2
RHEBL1	ENST00000550675.1 linkuse as main transcript	c.106G>C	p.Asp36His	missense_variant	2/5	5		ENSP00000447428.1	F8W1T5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251308

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135810

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461684

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727138

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

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

Mar 29, 2023

The c.106G>C (p.D36H) alteration is located in exon 2 (coding exon 2) of the RHEBL1 gene. This alteration results from a G to C substitution at nucleotide position 106, causing the aspartic acid (D) at amino acid position 36 to be replaced by a histidine (H). 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

0.33

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Uncertain

0.11

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.68

D;.

Eigen

Pathogenic

0.77

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.90

D;D

M_CAP

Benign

0.052

MetaRNN

Pathogenic

0.78

D;D

MetaSVM

Uncertain

0.27

MutationAssessor

Benign

1.3

L;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.54

PROVEAN

Pathogenic

-6.1

D;D

REVEL

Uncertain

0.61

Sift

Benign

0.15

T;T

Sift4G

Benign

0.13

T;.

Polyphen

0.99

D;D

Vest4

0.36

MutPred

0.51

Gain of glycosylation at T38 (P = 0.1141);Gain of glycosylation at T38 (P = 0.1141);

MVP

0.84

MPC

1.3

ClinPred

0.99

GERP RS

5.5

Varity_R

0.72

gMVP

0.57

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