NM_006712.5:c.1051G>C

Variant names:

• chr7-151077769-C-G
• rs773238430
• NM_006712.5:c.1051G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006712.5(FASTK):​c.1051G>C​(p.Ala351Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000277 in 1,444,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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: 0.0000028 (0 hom.)
• Consequence: FASTK NM_006712.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.70
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27876103).

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.1051G>C	p.Ala351Pro	missense	Exon 6 of 10	NP_006703.1	A0A090N8Z7
	FASTK	NM_001258461.2		c.970G>C	p.Ala324Pro	missense	Exon 6 of 10	NP_001245390.1	Q14296-3
	FASTK	NM_033015.4		c.628G>C	p.Ala210Pro	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.1051G>C	p.Ala351Pro	missense	Exon 6 of 10	ENSP00000297532.6	Q14296-1
	FASTK	ENST00000482571.2	TSL:1	c.970G>C	p.Ala324Pro	missense	Exon 6 of 10	ENSP00000418516.1	Q14296-3
	FASTK	ENST00000353841.6	TSL:1	c.628G>C	p.Ala210Pro	missense	Exon 5 of 9	ENSP00000324817.6	Q14296-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000164 AC: 4 AN: 243610 AF XY: 0.0000151

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000120

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000277 AC: 4 AN: 1444792 Hom.: 0 Cov.: 33 AF XY: 0.00000279 AC XY: 2 AN XY: 716178

African (AFR) AF: 0.00 AC: 0 AN: 33014

American (AMR) AF: 0.0000923 AC: 4 AN: 43316

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25534

East Asian (EAS) AF: 0.00 AC: 0 AN: 39322

South Asian (SAS) AF: 0.00 AC: 0 AN: 85304

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52546

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5682

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1100580

Other (OTH) AF: 0.00 AC: 0 AN: 59494

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000247 AC: 3

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	Uncertain	0.54
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L
PhyloP100		2.7
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.18
Sift	Benign	0.19	T
Sift4G	Uncertain	0.024	D
Polyphen		0.016	B
Vest4		0.65
MutPred		0.40		Gain of glycosylation at T348 (P = 0.0692)
MVP		0.45
MPC		1.4
ClinPred		0.17	T
GERP RS		1.8
Varity_R		0.23
gMVP		0.82
Mutation Taster		=80/20	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

dbSNP: rs773238430; hg19: chr7-150774856;