rs4453725
Positions:
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 8P and 16B. PVS1BP6_Very_StrongBA1
The ENST00000303698.7(NFU1):c.2T>A(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 1,603,608 control chromosomes in the GnomAD database, including 131,872 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.37 ( 10993 hom., cov: 32)
Exomes 𝑓: 0.40 ( 120879 hom. )
Consequence
NFU1
ENST00000303698.7 start_lost
ENST00000303698.7 start_lost
Scores
18
Clinical Significance
Conservation
PhyloP100: 0.886
Genes affected
NFU1 (HGNC:16287): (NFU1 iron-sulfur cluster scaffold) This gene encodes a protein that is localized to mitochondria and plays a critical role in iron-sulfur cluster biogenesis. The encoded protein assembles and transfers 4Fe-4S clusters to target apoproteins including succinate dehydrogenase and lipoic acid synthase. Mutations in this gene are a cause of multiple mitochondrial dysfunctions syndrome-1, and pseudogenes of this gene are located on the short arms of chromosomes 1 and 3. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
PVS1
?
Start lost variant, no new inframe start found.
BP6
?
Variant 2-69431994-A-T is Benign according to our data. Variant chr2-69431994-A-T is described in ClinVar as [Benign]. Clinvar id is 138516.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-69431994-A-T is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NFU1 | NM_001002755.4 | c.74T>A | p.Met25Lys | missense_variant | 2/8 | ENST00000410022.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NFU1 | ENST00000410022.7 | c.74T>A | p.Met25Lys | missense_variant | 2/8 | 1 | NM_001002755.4 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.372 AC: 56571AN: 151946Hom.: 10981 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.393 AC: 98476AN: 250802Hom.: 20057 AF XY: 0.395 AC XY: 53494AN XY: 135596
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GnomAD4 exome AF: 0.403 AC: 585644AN: 1451544Hom.: 120879 Cov.: 30 AF XY: 0.403 AC XY: 291496AN XY: 722826
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GnomAD4 genome ? AF: 0.372 AC: 56599AN: 152064Hom.: 10993 Cov.: 32 AF XY: 0.372 AC XY: 27643AN XY: 74342
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1607
ESP6500AA
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ClinVar
Significance: Benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 28, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 05, 2013 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Multiple mitochondrial dysfunctions syndrome 1 Benign:3
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 05, 2021 | - - |
not provided Benign:1
Benign, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Feb 19, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.
MutationTaster
Benign
P;P;P
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;D
Sift4G
Benign
T;D
Polyphen
B;B
Vest4
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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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