chr2-120285925-G-T

Variant names:

• chr2-120285925-G-T
• rs1690122539
• NM_002881.3:c.166G>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_002881.3(RALB):​c.166G>T​(p.Val56Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RALB NM_002881.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.98
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.866

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002881.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RALB	NM_002881.3	MANE Select	c.166G>T	p.Val56Phe	missense	Exon 3 of 5	NP_002872.1	P11234-1
	RALB	NM_001369400.1		c.166G>T	p.Val56Phe	missense	Exon 3 of 5	NP_001356329.1	P11234-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RALB	ENST00000272519.10	TSL:1 MANE Select	c.166G>T	p.Val56Phe	missense	Exon 3 of 5	ENSP00000272519.4	P11234-1
	RALB	ENST00000420510.5	TSL:2	c.166G>T	p.Val56Phe	missense	Exon 3 of 5	ENSP00000414224.1	P11234-1
	RALB	ENST00000862911.1		c.166G>T	p.Val56Phe	missense	Exon 3 of 5	ENSP00000532970.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.27
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.53	D
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D
M_CAP	Uncertain	0.093	D
MetaRNN	Pathogenic	0.87	D
MetaSVM	Uncertain	0.21	D
MutationAssessor	Benign	1.6	L
PhyloP100		8.0
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-3.1	D
REVEL	Pathogenic	0.76
Sift	Uncertain	0.013	D
Sift4G	Benign	0.099	T
Polyphen		0.68	P
Vest4		0.79
MutPred		0.48		Gain of ubiquitination at K53 (P = 0.0756)
MVP		0.92
MPC		1.3
ClinPred		0.97	D
GERP RS		5.0
Varity_R		0.60
gMVP		0.83
Mutation Taster		=23/77	disease causing

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

Other links and lift over

dbSNP: rs1690122539; hg19: chr2-121043501;