7-151077117-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006712.5(FASTK):c.1411C>G(p.Arg471Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: FASTK NM_006712.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.804

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.078256816).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FASTK	NM_006712.5	c.1411C>G	p.Arg471Gly	missense_variant	8/10	ENST00000297532.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FASTK	ENST00000297532.11	c.1411C>G	p.Arg471Gly	missense_variant	8/10	1	NM_006712.5	P1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 25, 2022

The c.1411C>G (p.R471G) alteration is located in exon 8 (coding exon 8) of the FASTK gene. This alteration results from a C to G substitution at nucleotide position 1411, causing the arginine (R) at amino acid position 471 to be replaced by a glycine (G). 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	Benign	0.052
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
Cadd	Benign	15
Dann	Benign	0.86
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.68	T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.078	T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.68	N;N;N
REVEL	Benign	0.030
Sift	Benign	0.043	D;D;T
Sift4G	Benign	0.41	T;T;T
Polyphen		0.0	.;B;.
Vest4		0.037
MutPred		0.27		.;Loss of MoRF binding (P = 0.0393);.;
MVP		0.37
MPC		0.77
ClinPred		0.093	T
GERP RS		2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.30

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-150774204; COSMIC: COSV99879799; COSMIC: COSV99879799;