Variant chr12-68652046-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 13 ACMG points: 13P and 0B. PS1PM1PM2PP3_StrongPP5

The NM_001010942.3(RAP1B):c.178G>C(p.Gly60Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 13/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Pathogenicin ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

RAP1B
NM_001010942.3 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 9.56

Variant links:

Genes affected

RAP1B (HGNC:9857): (RAP1B, member of RAS oncogene family) This gene encodes a member of the RAS-like small GTP-binding protein superfamily. Members of this family regulate multiple cellular processes including cell adhesion and growth and differentiation. This protein localizes to cellular membranes and has been shown to regulate integrin-mediated cell signaling. This protein also plays a role in regulating outside-in signaling in platelets. Alternate splicing results in multiple transcript variants. Pseudogenes of this gene are found on chromosomes 3, 5, 6 and 9. [provided by RefSeq, Oct 2011]

RAP1B links:

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 13 ACMG points.

PS1

Transcript NM_001010942.3 (RAP1B) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in ClinVar as 2674587

PM1

In a chain Ras-related protein Rap-1b (size 180) in uniprot entity RAP1B_HUMAN there are 5 pathogenic changes around while only 0 benign (100%) in NM_001010942.3

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.986

PP5

Variant 12-68652046-G-C is Pathogenic according to our data. Variant chr12-68652046-G-C is described in ClinVar as [Pathogenic]. Clinvar id is 2672307.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAP1B	NM_001010942.3 linkuse as main transcript	c.178G>C	p.Gly60Arg	missense_variant	4/8	ENST00000250559.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAP1B	ENST00000250559.14 linkuse as main transcript	c.178G>C	p.Gly60Arg	missense_variant	4/8	1	NM_001010942.3	P1	P61224-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Thrombocytopenia 11 with multiple congenital anomalies and dysmorphic facies

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Mar 06, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.52

BayesDel_noAF

Pathogenic

0.51

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Pathogenic

0.95

D;D;.;D;D;D;D;D;.;.;D;D;.;.;D;D;D

Eigen

Pathogenic

1.1

Eigen_PC

Pathogenic

0.97

FATHMM_MKL

Pathogenic

1.0

M_CAP

Pathogenic

0.43

MetaRNN

Pathogenic

0.99

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

MetaSVM

Pathogenic

1.1

MutationAssessor

Pathogenic

4.2

H;H;.;.;.;H;H;.;.;.;.;.;.;H;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D;D;D;D;D

PrimateAI

Pathogenic

0.90

PROVEAN

Pathogenic

-6.7

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

REVEL

Pathogenic

0.95

Sift

Pathogenic

0.0

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

Polyphen

1.0

D;D;.;.;.;D;D;.;.;.;.;.;.;.;.;.;.

Vest4

0.87

MutPred

0.93

Gain of phosphorylation at T61 (P = 0.1253);Gain of phosphorylation at T61 (P = 0.1253);Gain of phosphorylation at T61 (P = 0.1253);Gain of phosphorylation at T61 (P = 0.1253);Gain of phosphorylation at T61 (P = 0.1253);Gain of phosphorylation at T61 (P = 0.1253);Gain of phosphorylation at T61 (P = 0.1253);Gain of phosphorylation at T61 (P = 0.1253);.;Gain of phosphorylation at T61 (P = 0.1253);Gain of phosphorylation at T61 (P = 0.1253);Gain of phosphorylation at T61 (P = 0.1253);Gain of phosphorylation at T61 (P = 0.1253);Gain of phosphorylation at T61 (P = 0.1253);Gain of phosphorylation at T61 (P = 0.1253);Gain of phosphorylation at T61 (P = 0.1253);Gain of phosphorylation at T61 (P = 0.1253);

MVP

0.96

MPC

3.2

ClinPred

1.0

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Varity_R

0.96

gMVP

0.99

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over