rs145688619

Variant names:

• chr1-226940407-T-C
• rs145688619
• NM_020247.5:c.-10+8T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-226940407-T-C
• chr1-226940407-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_020247.5(COQ8A):​c.-10+8T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0129 in 152,262 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (39 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: COQ8A NM_020247.5 splice_region, intron
• Scores: Splicing: ADA: 0.0004773
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.335
• Publications: 0 publications found

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]

COQ8A Gene-Disease associations (from GenCC):

• autosomal recessive ataxia due to ubiquinone deficiency

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
• coenzyme Q10 deficiency

  Inheritance: AR Classification: DEFINITIVE Submitted by: Illumina

ENSG00000288674 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 1-226940407-T-C is Benign according to our data. Variant chr1-226940407-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 136305.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 = 0.0129 (1964/152262) while in subpopulation AFR AF = 0.0431 (1792/41568). AF 95% confidence interval is 0.0414. There are 39 homozygotes in GnomAd4. There are 936 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 39 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020247.5. 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
	COQ8A	NM_020247.5	MANE Select	c.-10+8T>C		splice_region intron	N/A	NP_064632.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COQ8A	ENST00000366777.4	TSL:1 MANE Select	c.-10+8T>C		splice_region intron	N/A	ENSP00000355739.3	Q8NI60-1
	COQ8A	ENST00000366778.5	TSL:1	c.-35+8T>C		splice_region intron	N/A	ENSP00000355740.1	Q8NI60-3
	ENSG00000288674	ENST00000366779.6	TSL:2	n.*4718+816T>C		intron	N/A	ENSP00000355741.2

Frequencies

GnomAD3 genomes AF: 0.0129 AC: 1960 AN: 152144 Hom.: 39 Cov.: 33

Gnomad AFR AF: 0.0431

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00628

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.0129

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 122 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 82

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 8

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 94

Other (OTH) AF: 0.00 AC: 0 AN: 12

GnomAD4 genome AF: 0.0129 AC: 1964 AN: 152262 Hom.: 39 Cov.: 33 AF XY: 0.0126 AC XY: 936 AN XY: 74468

African (AFR) AF: 0.0431 AC: 1792 AN: 41568

American (AMR) AF: 0.00627 AC: 96 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00432 AC: 15 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.0171 AC: 5 AN: 292

European-Non Finnish (NFE) AF: 0.000412 AC: 28 AN: 67986

Other (OTH) AF: 0.0128 AC: 27 AN: 2110

Alfa AF: 0.0105 Hom.: 2

Bravo AF: 0.0142

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Autosomal recessive ataxia due to ubiquinone deficiency (1)
-	-	1	Autosomal recessive cerebellar ataxia (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	14
DANN	Benign	0.77
PhyloP100		0.34
PromoterAI		0.23	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00048
dbscSNV1_RF	Benign	0.026
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

Other links and lift over

dbSNP: rs145688619; hg19: chr1-227128108;