Genetic Variant RALB:p.Ser10Arg (chr2-120278694-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002881.3(RALB):c.30C>A(p.Ser10Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,447,138 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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: 0.0000021 ( 0 hom. )

Consequence

RALB
NM_002881.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.978

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18148264).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RALB	NM_002881.3 link	c.30C>A	p.Ser10Arg	missense_variant	Exon 2 of 5	ENST00000272519.10	NP_002872.1	P11234-1A0A024RAG3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RALB	ENST00000272519.10 link	c.30C>A	p.Ser10Arg	missense_variant	Exon 2 of 5	1	NM_002881.3	ENSP00000272519.4		P11234-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000207

AC:

AN:

1447138

Hom.:

Cov.:

AF XY:

0.00000278

AC XY:

AN XY:

719420

show subpopulations

African (AFR)

AF:

0.0000303

AC:

AN:

32958

American (AMR)

AF:

0.00

AC:

AN:

42812

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25874

East Asian (EAS)

AF:

0.0000260

AC:

AN:

38490

South Asian (SAS)

AF:

0.00

AC:

AN:

84006

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53140

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5734

European-Non Finnish (NFE)

AF:

9.06e-7

AC:

AN:

1104290

Other (OTH)

AF:

0.00

AC:

AN:

59834

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 24, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.30C>A (p.S10R) alteration is located in exon 2 (coding exon 1) of the RALB gene. This alteration results from a C to A substitution at nucleotide position 30, causing the serine (S) at amino acid position 10 to be replaced by an arginine (R). 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

0.58

BayesDel_addAF

Benign

-0.031

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.063

T;T;T;.;T;T

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.12

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.87

D;.;D;D;D;D

M_CAP

Benign

0.039

MetaRNN

Benign

0.18

T;T;T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.82

.;L;L;.;.;.

PhyloP100

0.98

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.86

N;N;N;.;N;N

REVEL

Benign

0.054

Sift

Benign

0.035

D;T;T;.;T;T

Sift4G

Benign

0.11

T;T;T;T;T;T

Polyphen

0.056

.;B;B;.;.;.

Vest4

0.44, 0.37, 0.40

MutPred

0.34

.;Gain of MoRF binding (P = 0.0219);Gain of MoRF binding (P = 0.0219);Gain of MoRF binding (P = 0.0219);Gain of MoRF binding (P = 0.0219);Gain of MoRF binding (P = 0.0219);

MVP

0.79

MPC

1.0

ClinPred

0.57

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.10

gMVP

0.79

Mutation Taster

=59/41

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over