2-120289710-G-T

Variant names:

• chr2-120289710-G-T
• NM_002881.3:c.454G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002881.3(RALB):​c.454G>T​(p.Val152Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,774 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RALB NM_002881.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.89

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RALB	NM_002881.3	c.454G>T	p.Val152Leu	missense_variant	Exon 4 of 5	ENST00000272519.10	NP_002872.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RALB	ENST00000272519.10	c.454G>T	p.Val152Leu	missense_variant	Exon 4 of 5	1	NM_002881.3	ENSP00000272519.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461774 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727186

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T;T;T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	.;D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.71	D;D;D
MetaSVM	Benign	-0.54	T
MutationAssessor	Benign	0.34	N;N;.
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-2.4	N;N;N
REVEL	Uncertain	0.56
Sift	Uncertain	0.026	D;D;T
Sift4G	Benign	0.073	T;T;T
Polyphen		0.24	B;B;.
Vest4		0.88
MutPred		0.49		Loss of MoRF binding (P = 0.1021);Loss of MoRF binding (P = 0.1021);Loss of MoRF binding (P = 0.1021);
MVP		0.81
MPC		1.8
ClinPred		0.91	D
GERP RS		5.4
Varity_R		0.60
gMVP		0.66

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-121047286;