NM_004104.5:c.128_130delGGCinsATT

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_004104.5(FASN):​c.128_130delGGCinsATT​(p.GlyLeu43AspPhe) variant causes a missense, splice region change involving the alteration of a 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. G43G) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 34)

Consequence

FASN
NM_004104.5 missense, splice_region

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.53
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FASNNM_004104.5 linkc.128_130delGGCinsATT p.GlyLeu43AspPhe missense_variant, splice_region_variant ENST00000306749.4 NP_004095.4 P49327
FASNXM_011523538.3 linkc.128_130delGGCinsATT p.GlyLeu43AspPhe missense_variant, splice_region_variant XP_011521840.1 P49327

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FASNENST00000306749.4 linkc.128_130delGGCinsATT p.GlyLeu43AspPhe missense_variant, splice_region_variant 1 NM_004104.5 ENSP00000304592.2 P49327
FASNENST00000634990.1 linkc.128_130delGGCinsATT p.GlyLeu43AspPhe missense_variant, splice_region_variant 5 ENSP00000488964.1 A0A0U1RQF0
FASNENST00000635197.1 linkc.128_130delGGCinsATT p.GlyLeu43AspPhe missense_variant, splice_region_variant 3 ENSP00000489514.1 A0A0U1RRG3
FASNENST00000637525.1 linkn.-96_-94delGGCinsATT upstream_gene_variant 5

Frequencies

GnomAD3 genomes
Cov.:
34
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
Cov.:
34

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Epileptic encephalopathy Uncertain:1
Nov 11, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant, c.128_130delinsATT, is a complex sequence change that results in the deletion of 1 amino acid and insertion of 2 amino acid(s) in the FASN protein (p.Gly43_Leu44delinsAspPhe). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This variant has not been reported in the literature in individuals affected with FASN-related conditions. ClinVar contains an entry for this variant (Variation ID: 531064). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1555669729; hg19: chr17-80053346; API