rs140593847

Variant names:

• chr18-43115491-G-A
• rs140593847
• NM_002930.4:c.29C>T

Your query was ambiguous. Multiple possible variants found:

• chr18-43115491-G-A
• chr18-43115491-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002930.4(RIT2):​c.29C>T​(p.Ser10Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. 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. S10Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RIT2 NM_002930.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.64

Genes affected

RIT2 (HGNC:10017): (Ras like without CAAX 2) RIN belongs to the RAS (HRAS; MIM 190020) superfamily of small GTPases (Shao et al., 1999 [PubMed 10545207]).[supplied by OMIM, Mar 2008]

ENSG00000287209 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.116080016).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIT2	NM_002930.4	c.29C>T	p.Ser10Phe	missense_variant	Exon 1 of 5	ENST00000326695.10	NP_002921.1
RIT2	NM_001272077.2	c.29C>T	p.Ser10Phe	missense_variant	Exon 1 of 6		NP_001259006.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIT2	ENST00000326695.10	c.29C>T	p.Ser10Phe	missense_variant	Exon 1 of 5	1	NM_002930.4	ENSP00000321805.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000400 AC: 1 AN: 250200 Hom.: 0 AF XY: 0.00000739 AC XY: 1 AN XY: 135276

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000884

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.039	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.29	T;.;T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.20
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.69	T;T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.9	L;L;.
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.2	N;.;.
REVEL	Benign	0.058
Sift	Benign	0.16	T;.;.
Sift4G	Uncertain	0.011	D;D;D
Polyphen		0.17	B;B;.
Vest4		0.14
MutPred		0.24		Loss of phosphorylation at S10 (P = 0.0156);Loss of phosphorylation at S10 (P = 0.0156);Loss of phosphorylation at S10 (P = 0.0156);
MVP		0.87
MPC		0.62
ClinPred		0.30	T
GERP RS		2.5
Varity_R		0.048
gMVP		0.55

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

LitVar

Other links and lift over

dbSNP: rs140593847; hg19: chr18-40695456; COSMIC: COSV56307946;