7-151077663-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006712.5(FASTK):ā€‹c.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

Scores

2
12
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.32
Variant links:
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]

Genome browser will be placed here

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
FASTKNM_006712.5 linkuse as main transcriptc.1157T>G p.Phe386Cys missense_variant 6/10 ENST00000297532.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FASTKENST00000297532.11 linkuse as main transcriptc.1157T>G p.Phe386Cys missense_variant 6/101 NM_006712.5 P1Q14296-1

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152254
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.000145
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000184
AC:
4
AN:
217376
Hom.:
0
AF XY:
0.00000853
AC XY:
1
AN XY:
117208
show subpopulations
Gnomad AFR exome
AF:
0.000255
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000634
AC:
9
AN:
1420138
Hom.:
0
Cov.:
33
AF XY:
0.00000427
AC XY:
3
AN XY:
702678
show subpopulations
Gnomad4 AFR exome
AF:
0.000220
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000171
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152372
Hom.:
0
Cov.:
34
AF XY:
0.0000537
AC XY:
4
AN XY:
74510
show subpopulations
Gnomad4 AFR
AF:
0.000144
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000416
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000330
AC:
4

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 submitterclinical testingAmbry GeneticsFeb 06, 2023The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.95
BayesDel_addAF
Benign
-0.073
T
BayesDel_noAF
Uncertain
-0.050
CADD
Pathogenic
27
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.58
.;.;D;.
Eigen
Uncertain
0.53
Eigen_PC
Uncertain
0.52
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.88
D;D;D;D
M_CAP
Benign
0.041
D
MetaRNN
Uncertain
0.70
D;D;D;D
MetaSVM
Benign
-0.77
T
MutationAssessor
Benign
0.90
.;.;L;.
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Uncertain
0.74
T
PROVEAN
Uncertain
-4.3
.;D;D;D
REVEL
Uncertain
0.49
Sift
Uncertain
0.0020
.;D;D;D
Sift4G
Uncertain
0.0040
D;D;D;D
Polyphen
1.0
.;.;D;.
Vest4
0.85
MVP
0.70
MPC
1.9
ClinPred
0.77
D
GERP RS
4.3
Varity_R
0.48
gMVP
0.88

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs145223870; hg19: chr7-150774750; API