15-78991779-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001145648.3(RASGRF1):ā€‹c.3043G>Cā€‹(p.Ala1015Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,756 control chromosomes in the GnomAD database, with no homozygous occurrence. 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.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

RASGRF1
NM_001145648.3 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.577
Variant links:
Genes affected
RASGRF1 (HGNC:9875): (Ras protein specific guanine nucleotide releasing factor 1) The protein encoded by this gene is a guanine nucleotide exchange factor (GEF) similar to the Saccharomyces cerevisiae CDC25 gene product. Functional analysis has demonstrated that this protein stimulates the dissociation of GDP from RAS protein. The studies of the similar gene in mouse suggested that the Ras-GEF activity of this protein in brain can be activated by Ca2+ influx, muscarinic receptors, and G protein beta-gamma subunit. Mouse studies also indicated that the Ras-GEF signaling pathway mediated by this protein may be important for long-term memory. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Mar 2009]

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ACMG classification

Classification made for transcript

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=0.09420487).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RASGRF1NM_001145648.3 linkc.3043G>C p.Ala1015Pro missense_variant Exon 21 of 27 ENST00000558480.7 NP_001139120.1 Q8IUU5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RASGRF1ENST00000558480.7 linkc.3043G>C p.Ala1015Pro missense_variant Exon 21 of 27 2 NM_001145648.3 ENSP00000452781.2 Q13972-3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460756
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
726492
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
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
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
20
DANN
Benign
0.87
DEOGEN2
Benign
0.15
.;T;.
Eigen
Benign
-0.80
Eigen_PC
Benign
-0.73
FATHMM_MKL
Benign
0.75
D
LIST_S2
Benign
0.85
T;T;T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.094
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.2
.;L;.
PrimateAI
Uncertain
0.53
T
PROVEAN
Benign
-1.2
.;N;N
REVEL
Benign
0.020
Sift
Benign
0.19
.;T;T
Sift4G
Benign
0.13
T;T;T
Vest4
0.17
MVP
0.19
MPC
0.76
ClinPred
0.22
T
GERP RS
1.0
Varity_R
0.13
gMVP
0.61

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.

Other links and lift over

dbSNP: rs528237918; hg19: chr15-79284121; API