Genetic Variant RASIP1:p.Gly923Cys (chr19-48720923-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_017805.3(RASIP1):c.2767G>T(p.Gly923Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,566 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

RASIP1
NM_017805.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.44

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASIP1	NM_017805.3 link	c.2767G>T	p.Gly923Cys	missense_variant	Exon 12 of 12	ENST00000222145.9	NP_060275.2	Q5U651Q7L251Q8IUR2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASIP1	ENST00000222145.9 link	c.2767G>T	p.Gly923Cys	missense_variant	Exon 12 of 12	1	NM_017805.3	ENSP00000222145.3		Q5U651
RASIP1	ENST00000601530.1 link	n.1261G>T		non_coding_transcript_exon_variant	Exon 4 of 4	2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000798

AC:

AN:

250516

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135534

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461406

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727004

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000671

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 05, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2767G>T (p.G923C) alteration is located in exon 12 (coding exon 11) of the RASIP1 gene. This alteration results from a G to T substitution at nucleotide position 2767, causing the glycine (G) at amino acid position 923 to be replaced by a cysteine (C). 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

0.25

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.074

Eigen

Benign

0.030

Eigen_PC

Benign

-0.061

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.80

M_CAP

Benign

0.018

MetaRNN

Uncertain

0.43

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

PrimateAI

Uncertain

0.71

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.15

Sift

Benign

0.038

Sift4G

Uncertain

0.031

Polyphen

1.0

Vest4

0.52

MutPred

0.40

Loss of disorder (P = 0.0171);

MVP

0.24

MPC

1.1

ClinPred

0.90

GERP RS

5.6

Varity_R

0.23

gMVP

0.50

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

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