rs1481274971

Variant names:

• chr17-82087132-C-G
• rs1481274971
• NM_004104.5:c.3345G>C

Your query was ambiguous. Multiple possible variants found:

• chr17-82087132-C-G
• chr17-82087132-C-T

Variant summary

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

The NM_004104.5(FASN):​c.3345G>C​(p.Glu1115Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. E1115E) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FASN NM_004104.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.937
• 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

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.3345G>C	p.Glu1115Asp	missense	Exon 21 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.3345G>C	p.Glu1115Asp	missense	Exon 21 of 43	ENSP00000304592.2	P49327
	FASN	ENST00000940344.1		c.3372G>C	p.Glu1124Asp	missense	Exon 21 of 43	ENSP00000610403.1
	FASN	ENST00000940346.1		c.3369G>C	p.Glu1123Asp	missense	Exon 21 of 43	ENSP00000610405.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Epileptic encephalopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Benign	-0.024	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.67	D
Eigen	Benign	0.15
Eigen_PC	Benign	-0.061
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.61	D
MetaSVM	Benign	-0.42	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		0.94
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.32
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.013	D
Polyphen		1.0	D
Vest4		0.59
MutPred		0.44		Loss of catalytic residue at E1115 (P = 0.0248)
MVP		0.48
ClinPred		0.97	D
GERP RS		-0.40
Varity_R		0.73
gMVP		0.68

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

Other links and lift over

dbSNP: rs1481274971; hg19: chr17-80045008;