17-82082574-C-G

Position:

• chr17-82082574-C-G

Variant summary

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

The NM_004104.5(FASN):​c.5872G>C​(p.Glu1958Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E1958K) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FASN NM_004104.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.84

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.5872G>C	p.Glu1958Gln	missense_variant	34/43	ENST00000306749.4	NP_004095.4
FASN	XM_011523538.3	c.5872G>C	p.Glu1958Gln	missense_variant	34/43		XP_011521840.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FASN	ENST00000306749.4	c.5872G>C	p.Glu1958Gln	missense_variant	34/43	1	NM_004104.5	ENSP00000304592.2
FASN	ENST00000634990.1	c.5866G>C	p.Glu1956Gln	missense_variant	34/43	5		ENSP00000488964.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.33	T;.
Eigen	Benign	0.18
Eigen_PC	Benign	0.17
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.0080	T
MetaRNN	Uncertain	0.56	D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.56	N;.
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.2	N;.
REVEL	Benign	0.23
Sift	Benign	0.34	T;.
Sift4G	Benign	0.38	T;T
Polyphen		0.93	P;.
Vest4		0.52
MutPred		0.54		Loss of helix (P = 0.1706);.;
MVP		0.48
ClinPred		0.81	D
GERP RS		4.6
Varity_R		0.51
gMVP		0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs145688025; hg19: chr17-80040450;