rs2288648

Variant names:

• chr7-151077221-G-A
• rs2288648
• NM_006712.5:c.1307C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-151077221-G-A
• chr7-151077221-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 14/22 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 the same amino acid substitution has been previously reported as Likely benign in UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A436T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.037 (313 hom., cov: 34)
  • Exomes 𝑓: 0.011 (1145 hom.)
• Consequence: FASTK NM_006712.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.461

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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
FASTK	NM_006712.5	c.1307C>T	p.Ala436Val	missense_variant	Exon 8 of 10	ENST00000297532.11	NP_006703.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FASTK	ENST00000297532.11	c.1307C>T	p.Ala436Val	missense_variant	Exon 8 of 10	1	NM_006712.5	ENSP00000297532.6

Frequencies

GnomAD3 genomes AF: 0.0374 AC: 5688 AN: 152196 Hom.: 315 Cov.: 34

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

GnomAD2 exomes AF: 0.0291 AC: 7191 AN: 247120 AF XY: 0.0248

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 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.: 33 AF XY: 0.0105 AC XY: 7649 AN XY: 726388

Gnomad4 AFR exome AF: 0.0984 AC: 3293 AN: 33466

Gnomad4 AMR exome AF: 0.0431 AC: 1923 AN: 44652

Gnomad4 ASJ exome AF: 0.00111 AC: 29 AN: 26054

Gnomad4 EAS exome AF: 0.207 AC: 8203 AN: 39680

Gnomad4 SAS exome AF: 0.00728 AC: 628 AN: 86212

Gnomad4 FIN exome AF: 0.000380 AC: 20 AN: 52612

Gnomad4 NFE exome AF: 0.000794 AC: 883 AN: 1111504

Gnomad4 Remaining exome AF: 0.0184 AC: 1110 AN: 60352

GnomAD4 genome AF: 0.0374 AC: 5693 AN: 152314 Hom.: 313 Cov.: 34 AF XY: 0.0373 AC XY: 2776 AN XY: 74472

Gnomad4 AFR AF: 0.0973 AC: 0.0973111 AN: 0.0973111

Gnomad4 AMR AF: 0.0284 AC: 0.0284165 AN: 0.0284165

Gnomad4 ASJ AF: 0.00115 AC: 0.00115274 AN: 0.00115274

Gnomad4 EAS AF: 0.193 AC: 0.193305 AN: 0.193305

Gnomad4 SAS AF: 0.0106 AC: 0.010559 AN: 0.010559

Gnomad4 FIN AF: 0.000188 AC: 0.000188111 AN: 0.000188111

Gnomad4 NFE AF: 0.00124 AC: 0.00123519 AN: 0.00123519

Gnomad4 OTH AF: 0.0321 AC: 0.0321361 AN: 0.0321361

Alfa AF: 0.0166 Hom.: 266

Bravo AF: 0.0434

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.0899 AC: 396

ESP6500EA AF: 0.00174 AC: 15

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	T
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	N
LIST_S2	Benign	0.10	T;T;T;T
MetaRNN	Benign	0.0013	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	.;.;N;.
PrimateAI	Uncertain	0.67	T
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	T
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.024
gMVP		0.25
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2288648; hg19: chr7-150774308; COSMIC: COSV52540892; COSMIC: COSV52540892;