17-82083013-C-A

Variant names:

• chr17-82083013-C-A
• rs139792253
• NM_004104.5:c.5668G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004104.5(FASN):​c.5668G>T​(p.Ala1890Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 14/22 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. A1890T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FASN NM_004104.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.545
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FASN	NM_004104.5	c.5668G>T	p.Ala1890Ser	missense_variant	Exon 33 of 43	ENST00000306749.4	NP_004095.4
FASN	XM_011523538.3	c.5668G>T	p.Ala1890Ser	missense_variant	Exon 33 of 43		XP_011521840.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FASN	ENST00000306749.4	c.5668G>T	p.Ala1890Ser	missense_variant	Exon 33 of 43	1	NM_004104.5	ENSP00000304592.2
FASN	ENST00000634990.1	c.5662G>T	p.Ala1888Ser	missense_variant	Exon 33 of 43	5		ENSP00000488964.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	1.5
DANN	Uncertain	0.98
DEOGEN2	Benign	0.26	T;.
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.97
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.47	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.40	N;.
PhyloP100		0.55
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.010	N;.
REVEL	Benign	0.12
Sift	Uncertain	0.0040	D;.
Sift4G	Uncertain	0.020	D;D
Polyphen		0.0040	B;.
Vest4		0.28
MutPred		0.52		Gain of glycosylation at A1890 (P = 0.0931);.;
MVP		0.43
ClinPred		0.51	D
GERP RS		-4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
Varity_R		0.35
gMVP		0.51
Mutation Taster		=84/16	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: rs139792253; hg19: chr17-80040889;