FASN p.Tyr243*

Variant names:

• chr17-82092946-G-C
• NM_004104.5:c.729C>G
• FASN p.Tyr243*

Your query was ambiguous. Multiple possible variants found:

• chr17-82092946-G-C
• chr17-82092946-G-T

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_004104.5(FASN):​c.729C>G​(p.Tyr243*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Y243Y) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FASN NM_004104.5 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55
• Publications: 0 publications found

Genes affected

FASN (HGNC:3594): (fatty acid synthase) The enzyme encoded by this gene is a multifunctional protein. Its main function is to catalyze the synthesis of palmitate from acetyl-CoA and malonyl-CoA, in the presence of NADPH, into long-chain saturated fatty acids. In some cancer cell lines, this protein has been found to be fused with estrogen receptor-alpha (ER-alpha), in which the N-terminus of FAS is fused in-frame with the C-terminus of ER-alpha. [provided by RefSeq, Jul 2008]

FASN Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Pathogenic. The variant received 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004104.5. 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
	FASN	NM_004104.5	MANE Select	c.729C>G	p.Tyr243*	stop_gained	Exon 6 of 43	NP_004095.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FASN	ENST00000306749.4	TSL:1 MANE Select	c.729C>G	p.Tyr243*	stop_gained	Exon 6 of 43	ENSP00000304592.2	P49327
	FASN	ENST00000940344.1		c.756C>G	p.Tyr252*	stop_gained	Exon 6 of 43	ENSP00000610403.1
	FASN	ENST00000940346.1		c.729C>G	p.Tyr243*	stop_gained	Exon 6 of 43	ENSP00000610405.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.40	D
BayesDel_noAF	Pathogenic	0.33
CADD	Benign	16
DANN	Uncertain	0.99
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.61	D
PhyloP100		-1.5

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.34		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.34		Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr17-80050822;