rs200128097
Positions:
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_005006.7(NDUFS1):c.738-20A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000169 in 1,593,018 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000017 ( 0 hom. )
Consequence
NDUFS1
NM_005006.7 intron
NM_005006.7 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.300
Genes affected
NDUFS1 (HGNC:7707): (NADH:ubiquinone oxidoreductase core subunit S1) The protein encoded by this gene belongs to the complex I 75 kDa subunit family. Mammalian complex I is composed of 45 different subunits. It locates at the mitochondrial inner membrane. This protein has NADH dehydrogenase activity and oxidoreductase activity. It transfers electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. This protein is the largest subunit of complex I and it is a component of the iron-sulfur (IP) fragment of the enzyme. It may form part of the active site crevice where NADH is oxidized. Mutations in this gene are associated with complex I deficiency. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2011]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
?
Variant 2-206145046-T-A is Benign according to our data. Variant chr2-206145046-T-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 506815.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NDUFS1 | NM_005006.7 | c.738-20A>T | intron_variant | ENST00000233190.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NDUFS1 | ENST00000233190.11 | c.738-20A>T | intron_variant | 1 | NM_005006.7 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152188Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000165 AC: 4AN: 241698Hom.: 0 AF XY: 0.00000767 AC XY: 1AN XY: 130366
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GnomAD4 exome AF: 0.0000167 AC: 24AN: 1440830Hom.: 0 Cov.: 31 AF XY: 0.0000196 AC XY: 14AN XY: 713912
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152188Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74346
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 04, 2022 | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 506815). This variant has not been reported in the literature in individuals affected with NDUFS1-related conditions. This variant is present in population databases (rs200128097, gnomAD 0.004%). This sequence change falls in intron 8 of the NDUFS1 gene. It does not directly change the encoded amino acid sequence of the NDUFS1 protein. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 03, 2017 | 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. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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