8-124539527-G-C
Variant names:
Variant summary
Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_005005.3(NDUFB9):c.101+240G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0042 in 544,148 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.011 ( 28 hom., cov: 33)
Exomes 𝑓: 0.0015 ( 8 hom. )
Consequence
NDUFB9
NM_005005.3 intron
NM_005005.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.142
Genes affected
NDUFB9 (HGNC:7704): (NADH:ubiquinone oxidoreductase subunit B9) The protein encoded by this gene is a subunit of the mitochondrial oxidative phosphorylation complex I (nicotinamide adenine dinucleotide: ubiquinone oxidoreductase). Complex I is localized to the inner mitochondrial membrane and functions to dehydrogenate nicotinamide adenine dinucleotide and to shuttle electrons to coenzyme Q. Complex I deficiency is the most common defect found in oxidative phosphorylation disorders and results in a range of conditions, including lethal neonatal disease, hypertrophic cardiomyopathy, liver disease, and adult-onset neurodegenerative disorders. Pseudogenes of this gene are found on chromosomes five, seven and eight. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2015]
TATDN1 (HGNC:24220): (TatD DNase domain containing 1) Predicted to enable 3'-5'-exodeoxyribonuclease activity. Predicted to be involved in DNA metabolic process and nucleic acid phosphodiester bond hydrolysis. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant 8-124539527-G-C is Benign according to our data. Variant chr8-124539527-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1316727.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0112 (1703/152326) while in subpopulation AFR AF = 0.0385 (1601/41572). AF 95% confidence interval is 0.0369. There are 28 homozygotes in GnomAd4. There are 831 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position FAILED quality control check.
BS2
High Homozygotes in GnomAd4 at 28 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NDUFB9 | NM_005005.3 | c.101+240G>C | intron_variant | Intron 1 of 3 | ENST00000276689.8 | NP_004996.1 | ||
NDUFB9 | NM_001311168.2 | c.101+240G>C | intron_variant | Intron 1 of 3 | NP_001298097.1 | |||
NDUFB9 | NM_001278646.2 | c.-27+240G>C | intron_variant | Intron 1 of 3 | NP_001265575.1 | |||
NDUFB9 | NM_001278645.2 | c.-33+240G>C | intron_variant | Intron 1 of 3 | NP_001265574.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0111 AC: 1697AN: 152208Hom.: 28 Cov.: 33 show subpopulations
GnomAD3 genomes
AF:
AC:
1697
AN:
152208
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
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Gnomad NFE
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Gnomad OTH
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GnomAD4 exome AF: 0.00148 AC: 581AN: 391822Hom.: 8 AF XY: 0.00131 AC XY: 270AN XY: 205568 show subpopulations
GnomAD4 exome
AF:
AC:
581
AN:
391822
Hom.:
AF XY:
AC XY:
270
AN XY:
205568
Gnomad4 AFR exome
AF:
AC:
432
AN:
11254
Gnomad4 AMR exome
AF:
AC:
37
AN:
16690
Gnomad4 ASJ exome
AF:
AC:
0
AN:
12026
Gnomad4 EAS exome
AF:
AC:
0
AN:
26016
Gnomad4 SAS exome
AF:
AC:
10
AN:
42368
Gnomad4 FIN exome
AF:
AC:
1
AN:
24484
Gnomad4 NFE exome
AF:
AC:
21
AN:
234482
Gnomad4 Remaining exome
AF:
AC:
74
AN:
22804
Heterozygous variant carriers
0
28
56
85
113
141
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome Het
Exome Hom
Variant carriers
0
10
20
30
40
50
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome AF: 0.0112 AC: 1703AN: 152326Hom.: 28 Cov.: 33 AF XY: 0.0112 AC XY: 831AN XY: 74500 show subpopulations
GnomAD4 genome
AF:
AC:
1703
AN:
152326
Hom.:
Cov.:
33
AF XY:
AC XY:
831
AN XY:
74500
Gnomad4 AFR
AF:
AC:
0.0385115
AN:
0.0385115
Gnomad4 AMR
AF:
AC:
0.00476813
AN:
0.00476813
Gnomad4 ASJ
AF:
AC:
0
AN:
0
Gnomad4 EAS
AF:
AC:
0
AN:
0
Gnomad4 SAS
AF:
AC:
0.000207297
AN:
0.000207297
Gnomad4 FIN
AF:
AC:
0
AN:
0
Gnomad4 NFE
AF:
AC:
0.000191103
AN:
0.000191103
Gnomad4 OTH
AF:
AC:
0.00710227
AN:
0.00710227
Heterozygous variant carriers
0
86
172
259
345
431
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Genome Hom
Variant carriers
0
20
40
60
80
100
<30
30-35
35-40
40-45
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60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
8
AN:
3478
ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Jul 07, 2018
GeneDx
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:not provided
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
Mutation Taster
=100/0
polymorphism
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