1-226983786-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_020247.5(COQ8A):​c.1188C>T​(p.Asp396Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000273 in 1,613,030 control chromosomes in the GnomAD database, including 2 homozygotes. 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 0.00026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00027 ( 2 hom. )

Consequence

COQ8A
NM_020247.5 synonymous

Scores

2

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:6

Conservation

PhyloP100: -1.29
Variant links:
Genes affected
COQ8A (HGNC:16812): (coenzyme Q8A) This gene encodes a mitochondrial protein similar to yeast ABC1, which functions in an electron-transferring membrane protein complex in the respiratory chain. It is not related to the family of ABC transporter proteins. Expression of this gene is induced by the tumor suppressor p53 and in response to DNA damage, and inhibiting its expression partially suppresses p53-induced apoptosis. Alternatively spliced transcript variants have been found; however, their full-length nature has not been determined. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
Variant 1-226983786-C-T is Benign according to our data. Variant chr1-226983786-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 296018.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Uncertain_significance=2, Benign=1}. Variant chr1-226983786-C-T is described in Lovd as [Benign]. Variant chr1-226983786-C-T is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-1.29 with no splicing effect.
BS1
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.000275 (401/1460698) while in subpopulation MID AF= 0.0074 (42/5674). AF 95% confidence interval is 0.00563. There are 2 homozygotes in gnomad4_exome. There are 222 alleles in male gnomad4_exome subpopulation. Median coverage is 34. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
COQ8ANM_020247.5 linkuse as main transcriptc.1188C>T p.Asp396Asp synonymous_variant 10/15 ENST00000366777.4 NP_064632.2 Q8NI60-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
COQ8AENST00000366777.4 linkuse as main transcriptc.1188C>T p.Asp396Asp synonymous_variant 10/151 NM_020247.5 ENSP00000355739.3 Q8NI60-1
ENSG00000288674ENST00000366779.6 linkuse as main transcriptn.*5915C>T non_coding_transcript_exon_variant 27/322 ENSP00000355741.2
ENSG00000288674ENST00000366779.6 linkuse as main transcriptn.*5915C>T 3_prime_UTR_variant 27/322 ENSP00000355741.2

Frequencies

GnomAD3 genomes
AF:
0.000269
AC:
41
AN:
152214
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000965
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000654
Gnomad ASJ
AF:
0.000865
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.000282
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000250
Gnomad OTH
AF:
0.000957
GnomAD3 exomes
AF:
0.000381
AC:
95
AN:
249064
Hom.:
1
AF XY:
0.000488
AC XY:
66
AN XY:
135296
show subpopulations
Gnomad AFR exome
AF:
0.000126
Gnomad AMR exome
AF:
0.000377
Gnomad ASJ exome
AF:
0.000500
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000229
Gnomad FIN exome
AF:
0.000467
Gnomad NFE exome
AF:
0.000428
Gnomad OTH exome
AF:
0.00164
GnomAD4 exome
AF:
0.000275
AC:
401
AN:
1460698
Hom.:
2
Cov.:
34
AF XY:
0.000305
AC XY:
222
AN XY:
726684
show subpopulations
Gnomad4 AFR exome
AF:
0.000119
Gnomad4 AMR exome
AF:
0.000492
Gnomad4 ASJ exome
AF:
0.000306
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000301
Gnomad4 FIN exome
AF:
0.000611
Gnomad4 NFE exome
AF:
0.000208
Gnomad4 OTH exome
AF:
0.000580
GnomAD4 genome
AF:
0.000263
AC:
40
AN:
152332
Hom.:
0
Cov.:
33
AF XY:
0.000268
AC XY:
20
AN XY:
74500
show subpopulations
Gnomad4 AFR
AF:
0.0000962
Gnomad4 AMR
AF:
0.000588
Gnomad4 ASJ
AF:
0.000865
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.000282
Gnomad4 NFE
AF:
0.000250
Gnomad4 OTH
AF:
0.000947
Alfa
AF:
0.000442
Hom.:
0
Bravo
AF:
0.000298
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.000654
EpiControl
AF:
0.000948

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:6
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

not provided Benign:5
Benign, criteria provided, single submitterclinical testingAthena DiagnosticsOct 04, 2018- -
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenJul 01, 2022COQ8A: BP4, BP7 -
Likely benign, no assertion criteria providedclinical testingClinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center-- -
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 25, 2024- -
Likely benign, criteria provided, single submitterclinical testingGeneDxMar 05, 2021- -
Autosomal recessive cerebellar ataxia Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
Autosomal recessive ataxia due to ubiquinone deficiency Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -
not specified Benign:1
Benign, no assertion criteria providedclinical testingClinical Genetics, Academic Medical Center-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.55
CADD
Benign
6.4
DANN
Benign
0.77
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.8

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs139133094; hg19: chr1-227171487; API