chr12-64684884-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_178169.4(RASSF3):c.209A>G(p.Lys70Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000754 in 1,604,622 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 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000081 ( 0 hom. )
Consequence
RASSF3
NM_178169.4 missense
NM_178169.4 missense
Scores
6
7
Clinical Significance
Conservation
PhyloP100: 7.23
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 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.33074415).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RASSF3 | NM_178169.4 | c.209A>G | p.Lys70Arg | missense_variant | 2/5 | ENST00000542104.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RASSF3 | ENST00000542104.6 | c.209A>G | p.Lys70Arg | missense_variant | 2/5 | 1 | NM_178169.4 | P2 | |
RASSF3 | ENST00000637125.1 | c.392A>G | p.Lys131Arg | missense_variant | 3/6 | 5 | A2 | ||
RASSF3 | ENST00000283172.8 | c.209A>G | p.Lys70Arg | missense_variant, NMD_transcript_variant | 2/4 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152248Hom.: 0 Cov.: 32
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251054Hom.: 0 AF XY: 0.0000516 AC XY: 7AN XY: 135692
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GnomAD4 exome AF: 0.0000806 AC: 117AN: 1452374Hom.: 0 Cov.: 27 AF XY: 0.0000733 AC XY: 53AN XY: 723280
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152248Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74382
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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 | Mar 20, 2023 | The c.209A>G (p.K70R) alteration is located in exon 2 (coding exon 2) of the RASSF3 gene. This alteration results from a A to G substitution at nucleotide position 209, causing the lysine (K) at amino acid position 70 to be replaced by an arginine (R). 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
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;.
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
Polyphen
1.0
.;D;D
Vest4
0.44
MutPred
0.35
.;Loss of ubiquitination at K70 (P = 0.0224);Loss of ubiquitination at K70 (P = 0.0224);
MVP
0.37
MPC
0.37
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