Genetic Variant FASN:p.Ala340Ser (chr17-82092466-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_004104.5(FASN):c.1018G>T(p.Ala340Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000211 in 1,423,690 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

FASN
NM_004104.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.83

Publications

0 publications found

Variant links:

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

FASN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.1018G>T	p.Ala340Ser	missense	Exon 8 of 43	NP_004095.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FASN	ENST00000306749.4	TSL:1 MANE Select	c.1018G>T	p.Ala340Ser	missense	Exon 8 of 43	ENSP00000304592.2	P49327
FASN	ENST00000940344.1		c.1045G>T	p.Ala349Ser	missense	Exon 8 of 43	ENSP00000610403.1
FASN	ENST00000940346.1		c.1018G>T	p.Ala340Ser	missense	Exon 8 of 43	ENSP00000610405.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000550

AC:

AN:

181708

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000130

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000211

AC:

AN:

1423690

Hom.:

Cov.:

AF XY:

0.00000284

AC XY:

AN XY:

705274

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32898

American (AMR)

AF:

0.00

AC:

AN:

39198

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25480

East Asian (EAS)

AF:

0.00

AC:

AN:

37978

South Asian (SAS)

AF:

0.00

AC:

AN:

82114

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45996

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5242

European-Non Finnish (NFE)

AF:

0.00000274

AC:

AN:

1095742

Other (OTH)

AF:

0.00

AC:

AN:

59042

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Epileptic encephalopathy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.26

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.38

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.012

MetaRNN

Uncertain

0.43

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.0

PhyloP100

4.8

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.1

REVEL

Benign

0.26

Sift

Benign

0.55

Sift4G

Benign

0.83

Polyphen

0.77

Vest4

0.45

MutPred

0.76

Gain of disorder (P = 0.0332)

MVP

0.63

ClinPred

0.37

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.27

gMVP

0.75

Mutation Taster

=59/41

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over