rs148731010

Variant names:

• chr17-82082544-C-A
• NM_004104.5:c.5902G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-82082544-C-A
• chr17-82082544-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_004104.5(FASN):​c.5902G>T​(p.Val1968Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,456,196 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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: 0.0000014 (0 hom.)
• Consequence: FASN NM_004104.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.175

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.892

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FASN	NM_004104.5	c.5902G>T	p.Val1968Phe	missense_variant	Exon 34 of 43	ENST00000306749.4	NP_004095.4
FASN	XM_011523538.3	c.5902G>T	p.Val1968Phe	missense_variant	Exon 34 of 43		XP_011521840.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FASN	ENST00000306749.4	c.5902G>T	p.Val1968Phe	missense_variant	Exon 34 of 43	1	NM_004104.5	ENSP00000304592.2
FASN	ENST00000634990.1	c.5896G>T	p.Val1966Phe	missense_variant	Exon 34 of 43	5		ENSP00000488964.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1456196 Hom.: 0 Cov.: 38 AF XY: 0.00000138 AC XY: 1 AN XY: 724736

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: 8.99e-7

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Uncertain	0.075	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.68	D;.
Eigen	Benign	-0.69
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.65	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Benign	0.070	D
MetaRNN	Pathogenic	0.89	D;D
MetaSVM	Benign	-0.53	T
MutationAssessor	Pathogenic	3.1	M;.
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-3.0	D;.
REVEL	Uncertain	0.34
Sift	Uncertain	0.0040	D;.
Sift4G	Uncertain	0.0040	D;D
Polyphen		0.80	P;.
Vest4		0.82
MutPred		0.73		Loss of sheet (P = 0.1158);.;
MVP		0.85
ClinPred		0.98	D
GERP RS		-4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.4
Varity_R		0.86
gMVP		0.88

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: chr17-80040420;