chr7-151077221-G-A

Variant names:

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

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. 14/21 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 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
• Publications: 13 publications found

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

African (AFR) AF: 0.0984 AC: 3293 AN: 33466

American (AMR) AF: 0.0431 AC: 1923 AN: 44652

Ashkenazi Jewish (ASJ) AF: 0.00111 AC: 29 AN: 26054

East Asian (EAS) AF: 0.207 AC: 8203 AN: 39680

South Asian (SAS) AF: 0.00728 AC: 628 AN: 86212

European-Finnish (FIN) AF: 0.000380 AC: 20 AN: 52612

Middle Eastern (MID) AF: 0.0238 AC: 137 AN: 5766

European-Non Finnish (NFE) AF: 0.000794 AC: 883 AN: 1111504

Other (OTH) 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

African (AFR) AF: 0.0973 AC: 4046 AN: 41578

American (AMR) AF: 0.0284 AC: 435 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3470

East Asian (EAS) AF: 0.193 AC: 999 AN: 5168

South Asian (SAS) AF: 0.0106 AC: 51 AN: 4830

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10632

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00124 AC: 84 AN: 68006

Other (OTH) AF: 0.0321 AC: 68 AN: 2116

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;.
PhyloP100		-0.46
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

Other links and lift over

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