19-49635638-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006270.5(RRAS):​c.595C>A​(p.Pro199Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,094 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

RRAS
NM_006270.5 missense

Scores

8
11

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.00
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3557307).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RRASNM_006270.5 linkuse as main transcriptc.595C>A p.Pro199Thr missense_variant 6/6 ENST00000246792.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RRASENST00000246792.4 linkuse as main transcriptc.595C>A p.Pro199Thr missense_variant 6/61 NM_006270.5 P1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152094
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1300338
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
636102
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152094
Hom.:
0
Cov.:
31
AF XY:
0.0000135
AC XY:
1
AN XY:
74278
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Uncertain
0.092
D
BayesDel_noAF
Benign
-0.11
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.43
T
Eigen
Benign
0.081
Eigen_PC
Benign
0.095
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.95
D
M_CAP
Uncertain
0.12
D
MetaRNN
Benign
0.36
T
MetaSVM
Benign
-0.68
T
MutationAssessor
Benign
1.7
L
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.65
T
PROVEAN
Benign
-2.2
N
REVEL
Uncertain
0.42
Sift
Benign
0.20
T
Sift4G
Benign
0.36
T
Polyphen
0.94
P
Vest4
0.28
MutPred
0.32
Loss of catalytic residue at P199 (P = 0.0031);
MVP
0.85
MPC
1.2
ClinPred
0.95
D
GERP RS
4.0
Varity_R
0.13
gMVP
0.49

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1440723767; hg19: chr19-50138895; API