X-119871868-C-G
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_004541.4(NDUFA1):c.-44C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000126 in 1,186,833 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000070 ( 0 hom., 4 hem., cov: 25)
Exomes 𝑓: 0.0000065 ( 0 hom. 3 hem. )
Consequence
NDUFA1
NM_004541.4 5_prime_UTR
NM_004541.4 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.57
Genes affected
NDUFA1 (HGNC:7683): (NADH:ubiquinone oxidoreductase subunit A1) The human NDUFA1 gene codes for an essential component of complex I of the respiratory chain, which transfers electrons from NADH to ubiquinone. It has been noted that the N-terminal hydrophobic domain has the potential to be folded into an alpha-helix spanning the inner mitochondrial membrane with a C-terminal hydrophilic domain interacting with globular subunits of complex I. The highly conserved two-domain structure suggests that this feature is critical for the protein function and might act as an anchor for the NADH:ubiquinone oxidoreductase complex at the inner mitochondrial membrane. However, the NDUFA1 peptide is one of about 31 components of the "hydrophobic protein" (HP) fraction of complex I which is involved in proton translocation. Thus the NDUFA1 peptide may also participate in that function. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
Variant X-119871868-C-G is Benign according to our data. Variant chrX-119871868-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 512111.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Hemizygotes in GnomAd4 at 4 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NDUFA1 | NM_004541.4 | c.-44C>G | 5_prime_UTR_variant | 1/3 | ENST00000371437.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NDUFA1 | ENST00000371437.5 | c.-44C>G | 5_prime_UTR_variant | 1/3 | 1 | NM_004541.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000705 AC: 8AN: 113507Hom.: 0 Cov.: 25 AF XY: 0.000112 AC XY: 4AN XY: 35639
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GnomAD3 exomes AF: 0.0000218 AC: 4AN: 183366Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 67812
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GnomAD4 exome AF: 0.00000652 AC: 7AN: 1073326Hom.: 0 Cov.: 28 AF XY: 0.00000876 AC XY: 3AN XY: 342474
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GnomAD4 genome AF: 0.0000705 AC: 8AN: 113507Hom.: 0 Cov.: 25 AF XY: 0.000112 AC XY: 4AN XY: 35639
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 02, 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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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