12-26065199-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001394098.1(RASSF8):c.805G>A(p.Glu269Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000496 in 1,614,062 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Consequence
RASSF8
NM_001394098.1 missense
NM_001394098.1 missense
Scores
1
13
5
Clinical Significance
Conservation
PhyloP100: 5.19
Genes affected
RASSF8 (HGNC:13232): (Ras association domain family member 8) This gene encodes a member of the Ras-assocation domain family (RASSF) of tumor suppressor proteins. This gene is essential for maintaining adherens junction function in epithelial cells and has a role in epithelial cell migration. It is a lung tumor suppressor gene candidate. A chromosomal translocation t(12;22)(p11.2;q13.3) leading to the fusion of this gene and the FBLN1 gene is found in a complex type of synpolydactyly. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2011]
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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 |
---|---|---|---|---|---|---|---|
RASSF8 | NM_001394098.1 | c.805G>A | p.Glu269Lys | missense_variant | 4/6 | ENST00000689635.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RASSF8 | ENST00000689635.1 | c.805G>A | p.Glu269Lys | missense_variant | 4/6 | NM_001394098.1 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152210Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251222Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135776
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GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461852Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727220
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152210Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74364
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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 | Jun 23, 2023 | The c.805G>A (p.E269K) alteration is located in exon 3 (coding exon 2) of the RASSF8 gene. This alteration results from a G to A substitution at nucleotide position 805, causing the glutamic acid (E) at amino acid position 269 to be replaced by a lysine (K). 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
Uncertain
CADD
Uncertain
DANN
Pathogenic
DEOGEN2
Benign
.;T;.;T;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;.;.;.;D;.
M_CAP
Uncertain
D
MetaRNN
Uncertain
T;T;T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;M;M;M;M;M
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;.;N;N;N
REVEL
Uncertain
Sift
Uncertain
D;D;.;D;D;D
Sift4G
Uncertain
D;D;D;D;D;D
Polyphen
D;B;D;B;B;B
Vest4
MutPred
Gain of MoRF binding (P = 0.0016);Gain of MoRF binding (P = 0.0016);Gain of MoRF binding (P = 0.0016);Gain of MoRF binding (P = 0.0016);Gain of MoRF binding (P = 0.0016);Gain of MoRF binding (P = 0.0016);
MVP
MPC
0.73
ClinPred
D
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