5-1801432-G-A
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_ModerateBP6BS1
The NM_004553.6(NDUFS6):c.15G>A(p.Met5Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000255 in 1,605,202 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M5V) has been classified as Uncertain significance.
Frequency
Consequence
NM_004553.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NDUFS6 | NM_004553.6 | c.15G>A | p.Met5Ile | missense_variant | 1/4 | ENST00000274137.10 | |
MRPL36 | XM_011514080.3 | c.-66C>T | 5_prime_UTR_variant | 1/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NDUFS6 | ENST00000274137.10 | c.15G>A | p.Met5Ile | missense_variant | 1/4 | 1 | NM_004553.6 | P1 | |
NDUFS6 | ENST00000469176.1 | c.15G>A | p.Met5Ile | missense_variant | 1/3 | 2 | |||
NDUFS6 | ENST00000510329.1 | n.12G>A | non_coding_transcript_exon_variant | 1/2 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152258Hom.: 0 Cov.: 36
GnomAD3 exomes AF: 0.00000880 AC: 2AN: 227152Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 126170
GnomAD4 exome AF: 0.0000213 AC: 31AN: 1452826Hom.: 0 Cov.: 33 AF XY: 0.0000194 AC XY: 14AN XY: 722680
GnomAD4 genome AF: 0.0000656 AC: 10AN: 152376Hom.: 0 Cov.: 36 AF XY: 0.0000671 AC XY: 5AN XY: 74522
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 14, 2022 | This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 5 of the NDUFS6 protein (p.Met5Ile). This variant is present in population databases (rs374411074, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with NDUFS6-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. - |
Mitochondrial complex 1 deficiency, nuclear type 9 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | 3billion | Sep 20, 2024 | The homozygous variant was found in patients diagnosed with another variant in a different gene, with no symptoms related to the gene containing the homozygous variant. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at