chr2-120286070-C-G

Position:

• chr2-120286070-C-G

Variant summary

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

The ENST00000272519.10(RALB):​c.311C>G​(p.Thr104Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RALB ENST00000272519.10 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.05

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 (HGNC:):

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/exons	MANE	Protein	UniProt
RALB	NM_002881.3	c.311C>G	p.Thr104Ser	missense_variant	3/5	ENST00000272519.10	NP_002872.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RALB	ENST00000272519.10	c.311C>G	p.Thr104Ser	missense_variant	3/5	1	NM_002881.3	ENSP00000272519.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 23, 2024

The c.311C>G (p.T104S) alteration is located in exon 3 (coding exon 2) of the RALB gene. This alteration results from a C to G substitution at nucleotide position 311, causing the threonine (T) at amino acid position 104 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	Uncertain	0.41
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.53	D;D;D;T;D
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D;.;D;D;D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.69	D;D;D;D;D
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	0.72	.;N;N;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-2.5	N;D;D;N;D
REVEL	Uncertain	0.38
Sift	Benign	0.064	T;D;D;D;T
Sift4G	Benign	0.10	T;T;T;T;D
Polyphen		0.0	.;B;B;.;.
Vest4		0.60, 0.69
MutPred		0.51		.;Gain of disorder (P = 0.0455);Gain of disorder (P = 0.0455);Gain of disorder (P = 0.0455);Gain of disorder (P = 0.0455);
MVP		0.85
MPC		0.84
ClinPred		0.91	D
GERP RS		6.1
Varity_R		0.76
gMVP		0.53

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: chr2-121043646;