rs763379489

Positions:

• chr17-82088820-C-G
• chr17-82088820-C-T

Variant summary

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

The NM_004104.5(FASN):​c.2361G>C​(p.Lys787Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FASN NM_004104.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12

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]

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	Protein	UniProt
FASN	NM_004104.5	c.2361G>C	p.Lys787Asn	missense_variant	15/43	ENST00000306749.4	NP_004095.4
FASN	XM_011523538.3	c.2361G>C	p.Lys787Asn	missense_variant	15/43		XP_011521840.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FASN	ENST00000306749.4	c.2361G>C	p.Lys787Asn	missense_variant	15/43	1	NM_004104.5	ENSP00000304592	P1
FASN	ENST00000634990.1	c.2361G>C	p.Lys787Asn	missense_variant	15/43	5		ENSP00000488964

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.51	D;.
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.59	D;D
MetaSVM	Benign	-0.60	T
MutationAssessor	Pathogenic	2.9	M;.
MutationTaster	Benign	0.65	N
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-2.9	D;.
REVEL	Benign	0.19
Sift	Uncertain	0.010	D;.
Sift4G	Uncertain	0.0090	D;D
Polyphen		0.98	D;.
Vest4		0.48
MutPred		0.59		Loss of ubiquitination at K787 (P = 0.0134);Loss of ubiquitination at K787 (P = 0.0134);
MVP		0.62
ClinPred		0.98	D
GERP RS		3.1
Varity_R		0.58
gMVP		0.62

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

LitVar

Other links and lift over

dbSNP: rs763379489; hg19: chr17-80046696;