Variant chr7-151077221-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006712.5(FASTK):c.1307C>T(p.Ala436Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0136 in 1,612,612 control chromosomes in the GnomAD database, including 1,458 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.037 ( 313 hom., cov: 34)

Exomes 𝑓: 0.011 ( 1145 hom. )

Consequence

FASTK
NM_006712.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.461

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0012855828).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FASTK	NM_006712.5 linkuse as main transcript	c.1307C>T	p.Ala436Val	missense_variant	8/10	ENST00000297532.11	NP_006703.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FASTK	ENST00000297532.11 linkuse as main transcript	c.1307C>T	p.Ala436Val	missense_variant	8/10	1	NM_006712.5	ENSP00000297532	P1	Q14296-1

Frequencies

GnomAD3 genomes

AF:

0.0374

AC:

5688

AN:

152196

Hom.:

315

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0974

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0283

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.194

Gnomad SAS

AF:

0.0106

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00124

Gnomad OTH

AF:

0.0330

GnomAD3 exomes

AF:

0.0291

AC:

7191

AN:

247120

Hom.:

482

AF XY:

0.0248

AC XY:

3316

AN XY:

133960

show subpopulations

Gnomad AFR exome

AF:

0.101

Gnomad AMR exome

AF:

0.0445

Gnomad ASJ exome

AF:

0.00162

Gnomad EAS exome

AF:

0.195

Gnomad SAS exome

AF:

0.00737

Gnomad FIN exome

AF:

0.000466

Gnomad NFE exome

AF:

0.00124

Gnomad OTH exome

AF:

0.0157

GnomAD4 exome

AF:

0.0111

AC:

16226

AN:

1460298

Hom.:

1145

Cov.:

AF XY:

0.0105

AC XY:

7649

AN XY:

726388

show subpopulations

Gnomad4 AFR exome

AF:

0.0984

Gnomad4 AMR exome

AF:

0.0431

Gnomad4 ASJ exome

AF:

0.00111

Gnomad4 EAS exome

AF:

0.207

Gnomad4 SAS exome

AF:

0.00728

Gnomad4 FIN exome

AF:

0.000380

Gnomad4 NFE exome

AF:

0.000794

Gnomad4 OTH exome

AF:

0.0184

GnomAD4 genome

AF:

0.0374

AC:

5693

AN:

152314

Hom.:

313

Cov.:

AF XY:

0.0373

AC XY:

2776

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0973

Gnomad4 AMR

AF:

0.0284

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.193

Gnomad4 SAS

AF:

0.0106

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00124

Gnomad4 OTH

AF:

0.0321

Alfa

AF:

0.00973

Hom.:

Bravo

AF:

0.0434

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.0899

AC:

396

ESP6500EA

AF:

0.00174

AC:

ExAC

AF:

0.0288

AC:

3495

Asia WGS

AF:

0.0830

AC:

287

AN:

3478

EpiCase

AF:

0.00147

EpiControl

AF:

0.00166

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.034

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.71

CADD

Benign

6.1

DANN

Benign

0.81

DEOGEN2

Benign

0.044

.;.;T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.10

T;T;T;T

MetaRNN

Benign

0.0013

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

.;.;N;.

MutationTaster

Benign

1.0

P;P;P;P;P

PrimateAI

Uncertain

0.67

PROVEAN

Benign

1.9

.;N;N;N

REVEL

Benign

0.062

Sift

Benign

0.66

.;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0

.;.;B;.

Vest4

0.042

MPC

0.60

ClinPred

0.0018

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.024

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over