chr2-33558223-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001139488.2(RASGRP3):c.1592A>G(p.Asn531Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,459,128 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.000010 ( 0 hom. )
Consequence
RASGRP3
NM_001139488.2 missense
NM_001139488.2 missense
Scores
1
8
9
Clinical Significance
Conservation
PhyloP100: 9.24
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]
FAM98A (HGNC:24520): (family with sequence similarity 98 member A) Enables protein methyltransferase activity. Involved in positive regulation of cell population proliferation; positive regulation of gene expression; and protein methylation. Predicted to be part of tRNA-splicing ligase complex. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RASGRP3 | NM_001139488.2 | c.1592A>G | p.Asn531Ser | missense_variant | 16/18 | ENST00000403687.8 | |
RASGRP3-AS1 | NR_146505.1 | n.2497-2909T>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RASGRP3 | ENST00000403687.8 | c.1592A>G | p.Asn531Ser | missense_variant | 16/18 | 1 | NM_001139488.2 | P5 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD3 exomes AF: 0.00000409 AC: 1AN: 244612Hom.: 0 AF XY: 0.00000754 AC XY: 1AN XY: 132570
GnomAD3 exomes
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GnomAD4 exome AF: 0.0000103 AC: 15AN: 1459128Hom.: 0 Cov.: 31 AF XY: 0.00000965 AC XY: 7AN XY: 725498
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GnomAD4 genome ? Cov.: 31
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31
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3478
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 | Jun 26, 2023 | The c.1592A>G (p.N531S) alteration is located in exon 16 (coding exon 14) of the RASGRP3 gene. This alteration results from a A to G substitution at nucleotide position 1592, causing the asparagine (N) at amino acid position 531 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
Uncertain
D;D;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Benign
L;L;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Uncertain
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
P;P;.
Vest4
MutPred
Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);.;
MVP
MPC
0.49
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
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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