7-151077663-A-C
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_006712.5(FASTK):āc.1157T>Gā(p.Phe386Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000954 in 1,572,510 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000039 ( 0 hom., cov: 34)
Exomes š: 0.0000063 ( 0 hom. )
Consequence
FASTK
NM_006712.5 missense
NM_006712.5 missense
Scores
2
12
5
Clinical Significance
Conservation
PhyloP100: 8.32
Genes affected
FASTK (HGNC:24676): (Fas activated serine/threonine kinase) The protein encoded by this gene is a member of the serine/threonine protein kinase family. This kinase was shown to be activated rapidly during Fas-mediated apoptosis in Jurkat cells. In response to Fas receptor ligation, it phosphorylates TIA1, an apoptosis-promoting nuclear RNA-binding protein. The encoded protein is a strong inducer of lymphocyte apoptosis. Two transcript variants encoding different isoforms have been found for this gene. Other variants exist, but their full-length natures have not yet been determined. [provided by RefSeq, Jul 2008]
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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 |
---|---|---|---|---|---|---|---|
FASTK | NM_006712.5 | c.1157T>G | p.Phe386Cys | missense_variant | 6/10 | ENST00000297532.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FASTK | ENST00000297532.11 | c.1157T>G | p.Phe386Cys | missense_variant | 6/10 | 1 | NM_006712.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152254Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.0000184 AC: 4AN: 217376Hom.: 0 AF XY: 0.00000853 AC XY: 1AN XY: 117208
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GnomAD4 exome AF: 0.00000634 AC: 9AN: 1420138Hom.: 0 Cov.: 33 AF XY: 0.00000427 AC XY: 3AN XY: 702678
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GnomAD4 genome AF: 0.0000394 AC: 6AN: 152372Hom.: 0 Cov.: 34 AF XY: 0.0000537 AC XY: 4AN XY: 74510
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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 | Feb 06, 2023 | The c.1157T>G (p.F386C) alteration is located in exon 6 (coding exon 6) of the FASTK gene. This alteration results from a T to G substitution at nucleotide position 1157, causing the phenylalanine (F) at amino acid position 386 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
.;.;D;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
.;.;L;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
.;D;D;D
REVEL
Uncertain
Sift
Uncertain
.;D;D;D
Sift4G
Uncertain
D;D;D;D
Polyphen
1.0
.;.;D;.
Vest4
MVP
MPC
1.9
ClinPred
D
GERP RS
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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