chr2-33524042-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001139488.2(RASGRP3):c.680A>G(p.Asn227Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000514 in 1,613,836 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000053 ( 1 hom. )
Consequence
RASGRP3
NM_001139488.2 missense
NM_001139488.2 missense
Scores
5
13
Clinical Significance
Conservation
PhyloP100: 6.37
Genes affected
RASGRP3 (HGNC:14545): (RAS guanyl releasing protein 3) The protein encoded by this gene is a guanine nucleotide exchange factor that activates the oncogenes HRAS and RAP1A. Defects in this gene have been associated with systemic lupus erythematosus and several cancers. [provided by RefSeq, Mar 2017]
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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=0.11651945).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RASGRP3 | NM_001139488.2 | c.680A>G | p.Asn227Ser | missense_variant | 8/18 | ENST00000403687.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RASGRP3 | ENST00000403687.8 | c.680A>G | p.Asn227Ser | missense_variant | 8/18 | 1 | NM_001139488.2 | P5 | |
RASGRP3 | ENST00000402538.7 | c.680A>G | p.Asn227Ser | missense_variant | 9/19 | 1 | P5 | ||
RASGRP3 | ENST00000407811.5 | c.680A>G | p.Asn227Ser | missense_variant | 7/17 | 1 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152182Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000763 AC: 19AN: 249012Hom.: 0 AF XY: 0.000111 AC XY: 15AN XY: 135076
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GnomAD4 exome AF: 0.0000534 AC: 78AN: 1461536Hom.: 1 Cov.: 31 AF XY: 0.0000715 AC XY: 52AN XY: 727054
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GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152300Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74486
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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 05, 2022 | The c.680A>G (p.N227S) alteration is located in exon 8 (coding exon 6) of the RASGRP3 gene. This alteration results from a A to G substitution at nucleotide position 680, causing the asparagine (N) at amino acid position 227 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;T;.
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;N
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D
Sift4G
Benign
T;T;T
Polyphen
B;B;.
Vest4
MutPred
Loss of MoRF binding (P = 0.1235);Loss of MoRF binding (P = 0.1235);Loss of MoRF binding (P = 0.1235);
MVP
MPC
0.18
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at