chr7-151077630-C-G

Variant names:

• chr7-151077630-C-G
• NM_006712.5:c.1190G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006712.5(FASTK):​c.1190G>C​(p.Cys397Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000718 in 1,393,512 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: FASTK NM_006712.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.80
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24969918).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006712.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FASTK	NM_006712.5	MANE Select	c.1190G>C	p.Cys397Ser	missense	Exon 6 of 10	NP_006703.1	A0A090N8Z7
	FASTK	NM_001258461.2		c.1109G>C	p.Cys370Ser	missense	Exon 6 of 10	NP_001245390.1	Q14296-3
	FASTK	NM_033015.4		c.767G>C	p.Cys256Ser	missense	Exon 5 of 9	NP_148936.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FASTK	ENST00000297532.11	TSL:1 MANE Select	c.1190G>C	p.Cys397Ser	missense	Exon 6 of 10	ENSP00000297532.6	Q14296-1
	FASTK	ENST00000482571.2	TSL:1	c.1109G>C	p.Cys370Ser	missense	Exon 6 of 10	ENSP00000418516.1	Q14296-3
	FASTK	ENST00000353841.6	TSL:1	c.767G>C	p.Cys256Ser	missense	Exon 5 of 9	ENSP00000324817.6	Q14296-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.18e-7 AC: 1 AN: 1393512 Hom.: 0 Cov.: 33 AF XY: 0.00000146 AC XY: 1 AN XY: 685674

African (AFR) AF: 0.00 AC: 0 AN: 31234

American (AMR) AF: 0.00 AC: 0 AN: 35022

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21650

East Asian (EAS) AF: 0.00 AC: 0 AN: 39090

South Asian (SAS) AF: 0.00 AC: 0 AN: 75658

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50972

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5312

European-Non Finnish (NFE) AF: 9.28e-7 AC: 1 AN: 1077282

Other (OTH) AF: 0.00 AC: 0 AN: 57292

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	16
DANN	Benign	0.91
DEOGEN2	Benign	0.064	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.073
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		2.8
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.20	N
REVEL	Benign	0.094
Sift	Benign	0.22	T
Sift4G	Benign	0.61	T
Polyphen		0.0	B
Vest4		0.33
MutPred		0.61		Gain of disorder (P = 0.0092)
MVP		0.40
MPC		0.77
ClinPred		0.60	D
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.59
Mutation Taster		=81/19	polymorphism

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

Other links and lift over

hg19: chr7-150774717;