12-64694811-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.616G>C(p.Asp206His) variant causes a missense change. The variant allele was found at a frequency of 0.000519 in 1,614,058 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 0.00047 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00052 ( 0 hom. )
Consequence
RASSF3
NM_178169.4 missense
NM_178169.4 missense
Scores
6
7
Clinical Significance
Conservation
PhyloP100: 4.71
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=0.13245505).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RASSF3 | NM_178169.4 | c.616G>C | p.Asp206His | missense_variant | 5/5 | ENST00000542104.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RASSF3 | ENST00000542104.6 | c.616G>C | p.Asp206His | missense_variant | 5/5 | 1 | NM_178169.4 | P2 | |
RASSF3 | ENST00000637125.1 | c.799G>C | p.Asp267His | missense_variant | 6/6 | 5 | A2 | ||
RASSF3 | ENST00000283172.8 | c.*105G>C | 3_prime_UTR_variant, NMD_transcript_variant | 4/4 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000473 AC: 72AN: 152196Hom.: 0 Cov.: 32
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?
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GnomAD3 exomes AF: 0.000374 AC: 94AN: 251416Hom.: 0 AF XY: 0.000324 AC XY: 44AN XY: 135880
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GnomAD4 exome AF: 0.000523 AC: 765AN: 1461862Hom.: 0 Cov.: 31 AF XY: 0.000509 AC XY: 370AN XY: 727234
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GnomAD4 genome ? AF: 0.000473 AC: 72AN: 152196Hom.: 0 Cov.: 32 AF XY: 0.000336 AC XY: 25AN XY: 74352
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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 | Oct 13, 2021 | The c.616G>C (p.D206H) alteration is located in exon 5 (coding exon 5) of the RASSF3 gene. This alteration results from a G to C substitution at nucleotide position 616, causing the aspartic acid (D) at amino acid position 206 to be replaced by a histidine (H). 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
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;.
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
Polyphen
0.97
.;D;D
Vest4
0.49, 0.42
MVP
0.45
MPC
0.38
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
Score
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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