17-27582958-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001394583.1(KSR1):c.833G>A(p.Arg278Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000807 in 1,586,936 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 0.000059 ( 0 hom., cov: 25)
Exomes 𝑓: 0.000083 ( 0 hom. )
Consequence
KSR1
NM_001394583.1 missense
NM_001394583.1 missense
Scores
6
6
Clinical Significance
Conservation
PhyloP100: 5.37
Genes affected
KSR1 (HGNC:6465): (kinase suppressor of ras 1) Enables 14-3-3 protein binding activity; ATP binding activity; and protein C-terminus binding activity. Involved in positive regulation of MAPK cascade. Located in endoplasmic reticulum and membrane. Part of protein-containing complex. Implicated in breast adenocarcinoma. Biomarker of breast cancer. [provided by Alliance of Genome Resources, Apr 2022]
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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=0.2185362).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KSR1 | NM_001394583.1 | c.833G>A | p.Arg278Gln | missense_variant | 4/21 | ENST00000644974.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KSR1 | ENST00000644974.2 | c.833G>A | p.Arg278Gln | missense_variant | 4/21 | NM_001394583.1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000592 AC: 8AN: 135122Hom.: 0 Cov.: 25
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GnomAD3 exomes AF: 0.0000371 AC: 9AN: 242334Hom.: 0 AF XY: 0.0000227 AC XY: 3AN XY: 132426
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GnomAD4 exome AF: 0.0000827 AC: 120AN: 1451814Hom.: 0 Cov.: 42 AF XY: 0.0000789 AC XY: 57AN XY: 722414
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GnomAD4 genome ? AF: 0.0000592 AC: 8AN: 135122Hom.: 0 Cov.: 25 AF XY: 0.0000155 AC XY: 1AN XY: 64568
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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 26, 2022 | The c.422G>A (p.R141Q) alteration is located in exon 5 (coding exon 2) of the KSR1 gene. This alteration results from a G to A substitution at nucleotide position 422, causing the arginine (R) at amino acid position 141 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
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;D;D;.;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N
PrimateAI
Uncertain
T
Vest4
0.43
MVP
0.48
MPC
0.57
ClinPred
T
GERP RS
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