Variant 19-48721863-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_017805.3(RASIP1):c.2683G>A(p.Val895Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000436 in 1,605,980 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

RASIP1
NM_017805.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.63

Variant links:

Genes affected

RASIP1 (HGNC:24716): (Ras interacting protein 1) Enables GTPase binding activity and protein homodimerization activity. Involved in several processes, including negative regulation of Rho protein signal transduction; negative regulation of Rho-dependent protein serine/threonine kinase activity; and positive regulation of integrin activation. Located in cell-cell junction. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

RASIP1 links:

RASIP1 (HGNC:):

RASIP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.115300745).

BS2

High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RASIP1	NM_017805.3 linkuse as main transcript	c.2683G>A	p.Val895Met	missense_variant	11/12	ENST00000222145.9	NP_060275.2	Q5U651Q7L251Q8IUR2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RASIP1	ENST00000222145.9 linkuse as main transcript	c.2683G>A	p.Val895Met	missense_variant	11/12	1	NM_017805.3	ENSP00000222145.3		Q5U651
RASIP1	ENST00000601530.1 linkuse as main transcript	n.1177G>A		non_coding_transcript_exon_variant	3/4	2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152246

Hom.:

Cov.:

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

GnomAD3 exomes

AF:

0.00000416

AC:

AN:

240184

Hom.:

AF XY:

0.00

AC XY:

AN XY:

130882

show subpopulations

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:

0.00000928

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000413

AC:

AN:

1453734

Hom.:

Cov.:

AF XY:

0.00000553

AC XY:

AN XY:

723260

show subpopulations

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:

0.00000451

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152246

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74376

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

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 06, 2023

The c.2683G>A (p.V895M) alteration is located in exon 11 (coding exon 10) of the RASIP1 gene. This alteration results from a G to A substitution at nucleotide position 2683, causing the valine (V) at amino acid position 895 to be replaced by a methionine (M). 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

Benign

0.095

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.053

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.75

M_CAP

Benign

0.0095

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.71

REVEL

Benign

0.0090

Sift

Benign

0.082

Sift4G

Uncertain

0.029

Polyphen

0.14

Vest4

0.38

MVP

0.14

MPC

0.70

ClinPred

0.17

GERP RS

2.2

Varity_R

0.077

gMVP

0.28

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over