chr17-82083522-G-T

Position:

• chr17-82083522-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004104.5(FASN):​c.5336C>A​(p.Pro1779Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. 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. P1779A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: FASN NM_004104.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.31

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19854459).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FASN	NM_004104.5	c.5336C>A	p.Pro1779Gln	missense_variant	31/43	ENST00000306749.4
FASN	XM_011523538.3	c.5336C>A	p.Pro1779Gln	missense_variant	31/43

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FASN	ENST00000306749.4	c.5336C>A	p.Pro1779Gln	missense_variant	31/43	1	NM_004104.5	P1
FASN	ENST00000634990.1	c.5330C>A	p.Pro1777Gln	missense_variant	31/43	5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 34

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	13
DANN	Benign	0.83
DEOGEN2	Benign	0.40	T;.
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.50
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.86	D;D
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.20	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.37	N;.
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-2.3	N;.
REVEL	Benign	0.10
Sift	Benign	0.14	T;.
Sift4G	Benign	0.10	T;T
Polyphen		0.061	B;.
Vest4		0.19
MutPred		0.56		Gain of catalytic residue at P1779 (P = 0.0413);.;
MVP		0.40
ClinPred		0.20	T
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.054
gMVP		0.65

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

Publications

LitVar

Other links and lift over

dbSNP: rs2229426; hg19: chr17-80041398;