17-82085496-C-G

Variant names:

• chr17-82085496-C-G
• NM_004104.5:c.4108G>C

Variant summary

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

The NM_004104.5(FASN):​c.4108G>C​(p.Gly1370Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000694 in 1,441,084 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: FASN NM_004104.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0230

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=0.07591507).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FASN	NM_004104.5	c.4108G>C	p.Gly1370Arg	missense_variant	Exon 23 of 43	ENST00000306749.4	NP_004095.4
FASN	XM_011523538.3	c.4108G>C	p.Gly1370Arg	missense_variant	Exon 23 of 43		XP_011521840.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FASN	ENST00000306749.4	c.4108G>C	p.Gly1370Arg	missense_variant	Exon 23 of 43	1	NM_004104.5	ENSP00000304592.2
FASN	ENST00000634990.1	c.4102G>C	p.Gly1368Arg	missense_variant	Exon 23 of 43	5		ENSP00000488964.1
FASN	ENST00000579410.1	n.165G>C		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.94e-7 AC: 1 AN: 1441084 Hom.: 0 Cov.: 68 AF XY: 0.00 AC XY: 0 AN XY: 715086

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.07e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	12
DANN	Benign	0.69
DEOGEN2	Benign	0.25	T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.60	T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.076	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.3	L;.
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.31	N;.
REVEL	Benign	0.083
Sift	Benign	0.63	T;.
Sift4G	Benign	0.69	T;T
Polyphen		0.39	B;.
Vest4		0.17
MutPred		0.47		Gain of solvent accessibility (P = 0.0584);.;
MVP		0.21
ClinPred		0.11	T
GERP RS		-8.5
Varity_R		0.080
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-80043372;