chr12-64610662-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_178169.4(RASSF3):c.30G>C(p.Glu10Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000692 in 1,589,322 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000056 ( 0 hom. )
Consequence
RASSF3
NM_178169.4 missense
NM_178169.4 missense
Scores
1
2
16
Clinical Significance
Conservation
PhyloP100: -0.0150
Genes affected
RASSF3 (HGNC:14271): (Ras association domain family member 3) The RAS oncogene (MIM 190020) is mutated in nearly one-third of all human cancers. Members of the RAS superfamily are plasma membrane GTP-binding proteins that modulate intracellular signal transduction pathways. A subfamily of RAS effectors, including RASSF3, share a RAS association (RA) domain.[supplied by OMIM, Jul 2003]
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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=0.14216924).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RASSF3 | NM_178169.4 | c.30G>C | p.Glu10Asp | missense_variant | 1/5 | ENST00000542104.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RASSF3 | ENST00000542104.6 | c.30G>C | p.Glu10Asp | missense_variant | 1/5 | 1 | NM_178169.4 | P2 | |
RASSF3 | ENST00000637125.1 | c.294+68957G>C | intron_variant | 5 | A2 | ||||
RASSF3 | ENST00000540088.1 | n.141G>C | non_coding_transcript_exon_variant | 1/2 | 5 | ||||
RASSF3 | ENST00000283172.8 | c.30G>C | p.Glu10Asp | missense_variant, NMD_transcript_variant | 1/4 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152018Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000557 AC: 8AN: 1437304Hom.: 0 Cov.: 31 AF XY: 0.00000699 AC XY: 5AN XY: 715124
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152018Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74230
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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 | Dec 28, 2023 | The c.30G>C (p.E10D) alteration is located in exon 1 (coding exon 1) of the RASSF3 gene. This alteration results from a G to C substitution at nucleotide position 30, causing the glutamic acid (E) at amino acid position 10 to be replaced by an aspartic acid (D). 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
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;.
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
D;D
Vest4
MutPred
Loss of helix (P = 0.0444);Loss of helix (P = 0.0444);
MVP
MPC
0.40
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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