rs104894108
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_ModeratePS1_ModeratePM2
The NM_000144.5(FXN):c.3G>A(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
FXN
NM_000144.5 start_lost
NM_000144.5 start_lost
Scores
8
3
5
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 2.80
Genes affected
FXN (HGNC:3951): (frataxin) This nuclear gene encodes a mitochondrial protein which belongs to the FRATAXIN family. The protein functions in regulating mitochondrial iron transport and respiration. The expansion of intronic trinucleotide repeat GAA from 8-33 repeats to >90 repeats results in Friedreich ataxia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2016]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PVS1
Start lost variant, next in-frame start position is after 2 pathogenic variants. Next in-frame start position is after 225 CDS bases. Genomic position: 69046444. Lost 0.355 part of the original CDS.
PS1
Another start lost variant in NM_000144.5 (FXN) was described as [Pathogenic] in Lovd
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FXN | NM_000144.5 | c.3G>A | p.Met1? | start_lost | Exon 1 of 5 | ENST00000484259.3 | NP_000135.2 | |
FXN | NM_181425.3 | c.3G>A | p.Met1? | start_lost | Exon 1 of 5 | NP_852090.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FXN | ENST00000484259.3 | c.3G>A | p.Met1? | start_lost | Exon 1 of 5 | 3 | NM_000144.5 | ENSP00000419243.2 | ||
ENSG00000285130 | ENST00000642889.1 | c.3G>A | p.Met1? | start_lost | Exon 1 of 25 | ENSP00000493780.1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1357714Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 669456
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1357714
Hom.:
Cov.:
29
AF XY:
AC XY:
0
AN XY:
669456
Gnomad4 AFR exome
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Gnomad4 AMR exome
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Gnomad4 ASJ exome
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Gnomad4 EAS exome
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Gnomad4 SAS exome
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Gnomad4 FIN exome
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Gnomad4 OTH exome
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GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;.;T;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;D;D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D
MetaSVM
Pathogenic
D
PROVEAN
Benign
.;N;N;.;.;.
REVEL
Pathogenic
Sift
Pathogenic
.;D;D;.;.;.
Sift4G
Pathogenic
.;D;D;.;.;.
Polyphen
P;P;.;P;.;.
Vest4
0.84, 0.90
MutPred
Loss of disorder (P = 0.0292);Loss of disorder (P = 0.0292);Loss of disorder (P = 0.0292);Loss of disorder (P = 0.0292);Loss of disorder (P = 0.0292);Loss of disorder (P = 0.0292);
MVP
0.99
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at