chr5-1801445-C-T
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_004553.6(NDUFS6):c.28C>T(p.Leu10Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000482 in 1,452,816 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 Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. L10L) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 36)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Consequence
NDUFS6
NM_004553.6 synonymous
NM_004553.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.330
Publications
0 publications found
Genes affected
NDUFS6 (HGNC:7713): (NADH:ubiquinone oxidoreductase subunit S6) This gene encodes a subunit of the NADH:ubiquinone oxidoreductase (complex I), which is the first enzyme complex in the electron transport chain of mitochondria. This complex functions in the transfer of electrons from NADH to the respiratory chain. The subunit encoded by this gene is one of seven subunits in the iron-sulfur protein fraction. Mutations in this gene cause mitochondrial complex I deficiency, a disease that causes a wide variety of clinical disorders, including neonatal disease and adult-onset neurodegenerative disorders.[provided by RefSeq, Oct 2009]
MRPL36 (HGNC:14490): (mitochondrial ribosomal protein L36) Mammalian mitochondrial ribosomal proteins are encoded by nuclear genes and help in protein synthesis within the mitochondrion. Mitochondrial ribosomes (mitoribosomes) consist of a small 28S subunit and a large 39S subunit. They have an estimated 75% protein to rRNA composition compared to prokaryotic ribosomes, where this ratio is reversed. Another difference between mammalian mitoribosomes and prokaryotic ribosomes is that the latter contain a 5S rRNA. Among different species, the proteins comprising the mitoribosome differ greatly in sequence, and sometimes in biochemical properties, which prevents easy recognition by sequence homology. This gene encodes a 39S subunit protein. A pseudogene corresponding to this gene is found on chromosome 2p. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BP6
Variant 5-1801445-C-T is Benign according to our data. Variant chr5-1801445-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 730823.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.33 with no splicing effect.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_004553.6. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| NDUFS6 | NM_004553.6 | MANE Select | c.28C>T | p.Leu10Leu | synonymous | Exon 1 of 4 | NP_004544.1 | Q6IBC4 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| NDUFS6 | ENST00000274137.10 | TSL:1 MANE Select | c.28C>T | p.Leu10Leu | synonymous | Exon 1 of 4 | ENSP00000274137.6 | O75380 | |
| NDUFS6 | ENST00000933864.1 | c.28C>T | p.Leu10Leu | synonymous | Exon 1 of 4 | ENSP00000603923.1 | |||
| NDUFS6 | ENST00000469176.1 | TSL:2 | c.28C>T | p.Leu10Leu | synonymous | Exon 1 of 3 | ENSP00000422557.1 | D6RBT3 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
36
GnomAD2 exomes AF: 0.00 AC: 0AN: 227140 AF XY: 0.00
GnomAD2 exomes
AF:
AC:
0
AN:
227140
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
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Gnomad ASJ exome
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Gnomad EAS exome
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Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000482 AC: 7AN: 1452816Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 722752 show subpopulations
GnomAD4 exome
AF:
AC:
7
AN:
1452816
Hom.:
Cov.:
33
AF XY:
AC XY:
1
AN XY:
722752
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33388
American (AMR)
AF:
AC:
0
AN:
44566
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26038
East Asian (EAS)
AF:
AC:
0
AN:
39596
South Asian (SAS)
AF:
AC:
0
AN:
86040
European-Finnish (FIN)
AF:
AC:
0
AN:
46814
Middle Eastern (MID)
AF:
AC:
0
AN:
5716
European-Non Finnish (NFE)
AF:
AC:
7
AN:
1110586
Other (OTH)
AF:
AC:
0
AN:
60072
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
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Allele balance
Age Distribution
Exome Het
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GnomAD4 genome
GnomAD4 genome
Cov.:
36
Alfa
AF:
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Bravo
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ClinVar
ClinVar submissions
View on ClinVar Significance:Likely benign
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
-
1
not provided (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
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
Publications
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