Variant 2-120293190-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_002881.3(RALB):c.551A>G(p.Asn184Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,461,500 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 33)

Exomes 𝑓: 0.000012 ( 1 hom. )

Consequence

RALB
NM_002881.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.50

Variant links:

Genes affected

RALB (HGNC:9840): (RAS like proto-oncogene B) This gene encodes a GTP-binding protein that belongs to the small GTPase superfamily and Ras family of proteins. GTP-binding proteins mediate the transmembrane signaling initiated by the occupancy of certain cell surface receptors. [provided by RefSeq, Jul 2008]

RALB 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=0.09001559).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RALB	NM_002881.3 link	c.551A>G	p.Asn184Ser	missense_variant	5/5	ENST00000272519.10	NP_002872.1	P11234-1A0A024RAG3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RALB	ENST00000272519.10 link	c.551A>G	p.Asn184Ser	missense_variant	5/5	1	NM_002881.3	ENSP00000272519.4	P11234-1
RALB	ENST00000420510.5 link	c.551A>G	p.Asn184Ser	missense_variant	5/5	2		ENSP00000414224.1	P11234-1
RALB	ENST00000470417.1 link	n.445A>G		non_coding_transcript_exon_variant	5/5	3
RALB	ENST00000431732.5 link	n.*483A>G		downstream_gene_variant		5		ENSP00000393782.1	F8WEQ6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000116

AC:

AN:

1461500

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727060

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000936

Hom.:

Bravo

AF:

0.00000378

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

Jul 25, 2024

The c.551A>G (p.N184S) alteration is located in exon 5 (coding exon 4) of the RALB gene. This alteration results from a A to G substitution at nucleotide position 551, causing the asparagine (N) at amino acid position 184 to be replaced by a serine (S). 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

0.083

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.42

DEOGEN2

Benign

0.059

T;T

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.23

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.90

.;D

M_CAP

Benign

0.014

MetaRNN

Benign

0.090

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

-0.11

N;N

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.40

N;N

REVEL

Benign

0.27

Sift

Benign

0.91

T;T

Sift4G

Benign

0.90

T;T

Polyphen

0.0

B;B

Vest4

0.082

MutPred

0.29

Gain of phosphorylation at N184 (P = 0.0045);Gain of phosphorylation at N184 (P = 0.0045);

MVP

0.77

MPC

0.71

ClinPred

0.40

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.12

gMVP

0.27

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