7-151077011-G-A

Position:

• chr7-151077011-G-A

Variant summary

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

The NM_006712.5(FASTK):​c.1444C>T​(p.Arg482Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,460,192 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: FASTK NM_006712.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.939

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FASTK	NM_006712.5	c.1444C>T	p.Arg482Trp	missense_variant	9/10	ENST00000297532.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FASTK	ENST00000297532.11	c.1444C>T	p.Arg482Trp	missense_variant	9/10	1	NM_006712.5	P1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1460192 Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3 AN XY: 726424

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000384

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

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

Jun 07, 2024

The c.1444C>T (p.R482W) alteration is located in exon 9 (coding exon 9) of the FASTK gene. This alteration results from a C to T substitution at nucleotide position 1444, causing the arginine (R) at amino acid position 482 to be replaced by a tryptophan (W). 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	0.17
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.088	.;T;.
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.61	D
LIST_S2	Uncertain	0.93	D;D;D
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.61	D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	.;N;.
MutationTaster	Benign	0.60	D;D;D;D;D
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.8	N;N;N
REVEL	Benign	0.16
Sift	Uncertain	0.021	D;D;T
Sift4G	Uncertain	0.016	D;D;D
Polyphen		0.99	.;D;.
Vest4		0.52
MutPred		0.67		.;Loss of disorder (P = 0.0215);.;
MVP		0.59
MPC		1.5
ClinPred		0.75	D
GERP RS		3.2
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Varity_R		0.021
gMVP		0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: chr7-150774098;