chr17-82086429-C-T

Variant names:

• chr17-82086429-C-T
• NM_004104.5:c.3557G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004104.5(FASN):​c.3557G>A​(p.Cys1186Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,400 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 4.83

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3576332).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FASN	NM_004104.5	c.3557G>A	p.Cys1186Tyr	missense_variant	Exon 22 of 43	ENST00000306749.4	NP_004095.4
FASN	XM_011523538.3	c.3557G>A	p.Cys1186Tyr	missense_variant	Exon 22 of 43		XP_011521840.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FASN	ENST00000306749.4	c.3557G>A	p.Cys1186Tyr	missense_variant	Exon 22 of 43	1	NM_004104.5	ENSP00000304592.2
FASN	ENST00000634990.1	c.3557G>A	p.Cys1186Tyr	missense_variant	Exon 22 of 43	5		ENSP00000488964.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459400 Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1 AN XY: 726046

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: 0.0000195

Gnomad4 NFE exome AF: 0.00

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	Uncertain	0.39
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	19
DANN	Benign	0.68
DEOGEN2	Benign	0.29	T;.
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.33
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.36	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M;.
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.7	N;.
REVEL	Benign	0.093
Sift	Benign	0.47	T;.
Sift4G	Benign	1.0	T;T
Polyphen		0.038	B;.
Vest4		0.57
MutPred		0.39		Gain of catalytic residue at L1181 (P = 0.0874);Gain of catalytic residue at L1181 (P = 0.0874);
MVP		0.30
ClinPred		0.59	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.20
gMVP		0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: chr17-80044305;