16-19067678-G-GGGC

Position:

• chr16-19067678-G-GGGC

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PM4_Supporting BP6_Very_Strong BS1 BS2

The ENST00000321998.10(COQ7):​c.24_26dup​(p.Ala8dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00138 in 1,611,242 control chromosomes in the GnomAD database, including 21 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0069 (14 hom., cov: 33)
  • Exomes 𝑓: 0.00080 (7 hom.)
• Consequence: COQ7 ENST00000321998.10 inframe_insertion
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.40

Genes affected

COQ7 (HGNC:2244): (coenzyme Q7, hydroxylase) The protein encoded by this gene is similar to a mitochondrial di-iron containing hydroxylase in Saccharomyces cerevisiae that is involved with ubiquinone biosynthesis. Mutations in the yeast gene lead to slower development and longer life span. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2010]

COQ7-DT (HGNC:55362): (COQ7 divergent transcript)

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in ENST00000321998.10. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant 16-19067678-G-GGGC is Benign according to our data. Variant chr16-19067678-G-GGGC is described in ClinVar as [Benign]. Clinvar id is 1282807.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 = 0.00687 (1047/152328) while in subpopulation AFR AF= 0.0235 (979/41580). AF 95% confidence interval is 0.0223. There are 14 homozygotes in gnomad4. There are 501 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COQ7	NM_016138.5	c.24_26dup	p.Ala8dup	inframe_insertion	1/6	ENST00000321998.10	NP_057222.2
COQ7-DT	NR_119381.1	n.13_14insGCC		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COQ7	ENST00000321998.10	c.24_26dup	p.Ala8dup	inframe_insertion	1/6	1	NM_016138.5	ENSP00000322316	P1

Frequencies

GnomAD3 genomes AF: 0.00687 AC: 1045 AN: 152210 Hom.: 14 Cov.: 33

Gnomad AFR AF: 0.0236

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00307

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00174 AC: 418 AN: 239666 Hom.: 5 AF XY: 0.00146 AC XY: 191 AN XY: 131212

Gnomad AFR exome AF: 0.0219

Gnomad AMR exome AF: 0.00174

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000564

Gnomad SAS exome AF: 0.0000656

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000254

Gnomad OTH exome AF: 0.00102

GnomAD4 exome AF: 0.000803 AC: 1171 AN: 1458914 Hom.: 7 Cov.: 30 AF XY: 0.000707 AC XY: 513 AN XY: 725784

Gnomad4 AFR exome AF: 0.0234

Gnomad4 AMR exome AF: 0.00194

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.0000190

Gnomad4 NFE exome AF: 0.000178

Gnomad4 OTH exome AF: 0.00151

GnomAD4 genome AF: 0.00687 AC: 1047 AN: 152328 Hom.: 14 Cov.: 33 AF XY: 0.00673 AC XY: 501 AN XY: 74490

Gnomad4 AFR AF: 0.0235

Gnomad4 AMR AF: 0.00307

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.00284

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 06, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs531281193; hg19: chr16-19079000;