1-32868221-ACG-GCA

Variant names:

• chr1-32868221-ACG-GCA
• NM_153756.3:c.376_378delCGTinsTGC
• FNDC5 p.Arg126Cys

Variant summary

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

The NM_153756.3(FNDC5):​c.376_378delCGTinsTGC​(p.Arg126Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R126L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FNDC5 NM_153756.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.59
• Publications: 0 publications found

Genes affected

FNDC5 (HGNC:20240): (fibronectin type III domain containing 5) This gene encodes a secreted protein that is released from muscle cells during exercise. The encoded protein may participate in the development of brown fat. Translation of the precursor protein initiates at a non-AUG start codon at a position that is conserved as an AUG start codon in other organisms. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2013]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153756.3. 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
	FNDC5	NM_153756.3	MANE Select	c.376_378delCGTinsTGC	p.Arg126Cys	missense	N/A	NP_715637.2	A0A0A0MRR6
	FNDC5	NM_001441683.1		c.520_522delCGTinsTGC	p.Arg174Cys	missense	N/A	NP_001428612.1
	FNDC5	NM_001436107.1		c.376_378delCGTinsTGC	p.Arg126Cys	missense	N/A	NP_001423036.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FNDC5	ENST00000373471.9	TSL:2 MANE Select	c.376_378delCGTinsTGC	p.Arg126Cys	missense	N/A	ENSP00000362570.5	A0A0A0MRR6
	FNDC5	ENST00000496770.1	TSL:1	c.151_153delCGTinsTGC	p.Arg51Cys	missense	N/A	ENSP00000476320.1	Q8NAU1-3
	FNDC5	ENST00000710568.1		c.520_522delCGTinsTGC	p.Arg174Cys	missense	N/A	ENSP00000518350.1	Q8NAU1-5

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.6

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-33333822;