Variant 22-23692491-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000290691.10(RGL4):c.336G>C(p.Gln112His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 0.0000048 ( 0 hom. )

Consequence

RGL4
ENST00000290691.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.38

Variant links:

Genes affected

RGL4 (HGNC:31911): (ral guanine nucleotide dissociation stimulator like 4) This oncogene encodes a protein similar to guanine nucleotide exchange factor Ral guanine dissociation stimulator. Increased expression of this gene leads to translocation of the encoded protein to the cell membrane. The encoded protein can activate several pathways, including the Ras-Raf-MEK-ERK cascade. [provided by RefSeq, Jul 2016]

RGL4 links:

ENSG00000291299 (HGNC:):

ENSG00000291299 links:

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ACMG classification

Classification made for transcript

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=0.18937606).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGL4	NM_153615.2 linkuse as main transcript	c.336G>C	p.Gln112His	missense_variant	2/11	ENST00000290691.10	NP_705843.1	Q8IZJ4-1
RGL4	NM_001329424.3 linkuse as main transcript	c.336G>C	p.Gln112His	missense_variant	2/12		NP_001316353.1	Q8IZJ4Q3ZCN2
GUSBP11	NR_024448.2 linkuse as main transcript	n.2561+1628C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGL4	ENST00000290691.10 linkuse as main transcript	c.336G>C	p.Gln112His	missense_variant	2/11	1	NM_153615.2	ENSP00000290691.5		Q8IZJ4-1
RGL4	ENST00000441897.5 linkuse as main transcript	n.336G>C		non_coding_transcript_exon_variant	4/14	2		ENSP00000396252.1		E9PH21

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461804

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727186

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

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 28, 2024

The c.336G>C (p.Q112H) alteration is located in exon 2 (coding exon 2) of the RGL4 gene. This alteration results from a G to C substitution at nucleotide position 336, causing the glutamine (Q) at amino acid position 112 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

0.30

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0097

T;.

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.77

T;T

M_CAP

Benign

0.0020

MetaRNN

Benign

0.19

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.21

Sift

Benign

0.20

T;T

Sift4G

Benign

0.079

T;T

Polyphen

1.0

D;.

Vest4

0.18

MutPred

0.39

Loss of disorder (P = 0.1446);Loss of disorder (P = 0.1446);

MVP

0.46

MPC

0.071

ClinPred

0.45

GERP RS

-4.4

Varity_R

0.073

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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