rs766259420

Variant names:

• chr19-49636830-C-A
• rs766259420
• NM_006270.5:c.338G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-49636830-C-A
• chr19-49636830-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006270.5(RRAS):​c.338G>T​(p.Arg113Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R113Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: RRAS NM_006270.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.61
• Publications: 0 publications found

Genes affected

RRAS (HGNC:10447): (RAS related) The protein encoded by this gene is a small GTPase involved in diverse processes including angiogenesis, vascular homeostasis and regeneration, cell adhesion, and neuronal axon guidance. Mutations in this gene are found in many invasive cancers. [provided by RefSeq, Jul 2015]

RRAS Gene-Disease associations (from GenCC):

• Noonan syndrome and Noonan-related syndrome

  Inheritance: AD Classification: STRONG Submitted by: G2P
• Noonan syndrome

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: ClinGen, Genomics England PanelApp

ACMG classification

Our verdict: Uncertain_significance. The variant received 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
RRAS	NM_006270.5	c.338G>T	p.Arg113Leu	missense_variant	Exon 3 of 6	ENST00000246792.4	NP_006261.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RRAS	ENST00000246792.4	c.338G>T	p.Arg113Leu	missense_variant	Exon 3 of 6	1	NM_006270.5	ENSP00000246792.2
RRAS	ENST00000601532.1	n.478G>T		non_coding_transcript_exon_variant	Exon 2 of 4	5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 40

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Uncertain	0.050	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.83	D
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.093
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	1.4	L
PhyloP100		4.6
PrimateAI	Uncertain	0.75	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Uncertain	0.41
Sift	Benign	0.047	D
Sift4G	Benign	0.11	T
Polyphen		0.88	P
Vest4		0.67
MutPred		0.42		Loss of solvent accessibility (P = 0.0217);
MVP		0.96
MPC		0.76
ClinPred		0.97	D
GERP RS		1.4
Varity_R		0.37
gMVP		0.65
Mutation Taster		=59/41	polymorphism

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: rs766259420; hg19: chr19-50140087;