1-32868337-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_153756.3(FNDC5):c.262C>T(p.Arg88Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000062 ( 0 hom. )
Consequence
FNDC5
NM_153756.3 missense
NM_153756.3 missense
Scores
5
9
3
Clinical Significance
Conservation
PhyloP100: 9.24
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FNDC5 | NM_153756.3 | c.262C>T | p.Arg88Cys | missense_variant | 3/6 | ENST00000373471.9 | NP_715637.2 | |
FNDC5 | NM_001171940.2 | c.262C>T | p.Arg88Cys | missense_variant | 3/6 | NP_001165411.2 | ||
FNDC5 | NM_001171941.3 | c.37C>T | p.Arg13Cys | missense_variant | 3/5 | NP_001165412.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FNDC5 | ENST00000373471.9 | c.262C>T | p.Arg88Cys | missense_variant | 3/6 | 2 | NM_153756.3 | ENSP00000362570 | ||
FNDC5 | ENST00000496770.1 | c.37C>T | p.Arg13Cys | missense_variant | 3/5 | 1 | ENSP00000476320 | |||
FNDC5 | ENST00000710568.1 | c.406C>T | p.Arg136Cys | missense_variant | 3/6 | ENSP00000518350 | P1 | |||
FNDC5 | ENST00000649537.2 | c.229C>T | p.Arg77Cys | missense_variant | 3/6 | ENSP00000497837 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
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32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251282Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135822
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GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461864Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727232
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GnomAD4 genome Cov.: 32
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32
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 06, 2023 | The c.37C>T (p.R13C) alteration is located in exon 3 (coding exon 1) of the FNDC5 gene. This alteration results from a C to T substitution at nucleotide position 37, causing the arginine (R) at amino acid position 13 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
.;.;M;.
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
REVEL
Uncertain
Sift4G
Pathogenic
D;.;.;D
Polyphen
1.0
.;.;.;D
Vest4
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at