Genetic Variant FASTK:p.Arg396His (chr7-151077633-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006712.5(FASTK):c.1187G>A(p.Arg396His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000323 in 1,545,986 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

FASTK
NM_006712.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.39

Publications

0 publications found

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]

FASTK links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1673713).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006712.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FASTK	NM_006712.5	MANE Select	c.1187G>A	p.Arg396His	missense	Exon 6 of 10	NP_006703.1	A0A090N8Z7
FASTK	NM_001258461.2		c.1106G>A	p.Arg369His	missense	Exon 6 of 10	NP_001245390.1	Q14296-3
FASTK	NM_033015.4		c.764G>A	p.Arg255His	missense	Exon 5 of 9	NP_148936.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FASTK	ENST00000297532.11	TSL:1 MANE Select	c.1187G>A	p.Arg396His	missense	Exon 6 of 10	ENSP00000297532.6	Q14296-1
FASTK	ENST00000482571.2	TSL:1	c.1106G>A	p.Arg369His	missense	Exon 6 of 10	ENSP00000418516.1	Q14296-3
FASTK	ENST00000353841.6	TSL:1	c.764G>A	p.Arg255His	missense	Exon 5 of 9	ENSP00000324817.6	Q14296-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

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

GnomAD2 exomes

AF:

0.0000101

AC:

AN:

197270

AF XY:

0.00000950

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000109

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000287

AC:

AN:

1393738

Hom.:

Cov.:

AF XY:

0.00000292

AC XY:

AN XY:

685868

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31234

American (AMR)

AF:

0.00

AC:

AN:

34952

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21732

East Asian (EAS)

AF:

0.00

AC:

AN:

39082

South Asian (SAS)

AF:

0.0000132

AC:

AN:

75710

European-Finnish (FIN)

AF:

0.0000196

AC:

AN:

51002

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5332

European-Non Finnish (NFE)

AF:

0.00000186

AC:

AN:

1077414

Other (OTH)

AF:

0.00

AC:

AN:

57280

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152248

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41476

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000826

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.16

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.093

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.0067

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

3.4

PrimateAI

Benign

0.42

PROVEAN

Benign

0.0

REVEL

Benign

0.090

Sift

Benign

0.55

Sift4G

Benign

0.074

Polyphen

0.012

Vest4

0.39

MutPred

0.58

Loss of MoRF binding (P = 0.0779)

MVP

0.59

MPC

0.81

ClinPred

0.20

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.068

gMVP

0.59

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over