NM_016138.5:c.24_26dupGGC

Variant names:

• chr16-19067678-G-GGGC
• rs531281193
• NM_016138.5:c.24_26dupGGC

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 1P and 16B. PM4_Supporting BP6_Very_Strong BS1 BS2

The NM_016138.5(COQ7):​c.24_26dupGGC​(p.Ala9dup) variant causes a disruptive 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 NM_016138.5 disruptive_inframe_insertion
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.40
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -15 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_016138.5. 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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 14 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016138.5. 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
	COQ7	NM_016138.5	MANE Select	c.24_26dupGGC	p.Ala9dup	disruptive_inframe_insertion	Exon 1 of 6	NP_057222.2
	COQ7	NM_001370490.1		c.24_26dupGGC	p.Ala9dup	disruptive_inframe_insertion	Exon 1 of 5	NP_001357419.1
	COQ7-DT	NR_119379.1		n.11_13dupGCC		non_coding_transcript_exon	Exon 1 of 4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COQ7	ENST00000321998.10	TSL:1 MANE Select	c.24_26dupGGC	p.Ala9dup	disruptive_inframe_insertion	Exon 1 of 6	ENSP00000322316.5	Q99807-1
	COQ7	ENST00000568985.5	TSL:2	c.24_26dupGGC	p.Ala9dup	disruptive_inframe_insertion	Exon 1 of 7	ENSP00000456734.1	Q99807-1
	COQ7	ENST00000937633.1		c.24_26dupGGC	p.Ala9dup	disruptive_inframe_insertion	Exon 1 of 4	ENSP00000607692.1

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

GnomAD2 exomes AF: 0.00174 AC: 418 AN: 239666 AF XY: 0.00146

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 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

African (AFR) AF: 0.0234 AC: 782 AN: 33384

American (AMR) AF: 0.00194 AC: 86 AN: 44390

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26052

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39656

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86158

European-Finnish (FIN) AF: 0.0000190 AC: 1 AN: 52626

Middle Eastern (MID) AF: 0.00122 AC: 7 AN: 5756

European-Non Finnish (NFE) AF: 0.000178 AC: 198 AN: 1110704

Other (OTH) AF: 0.00151 AC: 91 AN: 60188

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

African (AFR) AF: 0.0235 AC: 979 AN: 41580

American (AMR) AF: 0.00307 AC: 47 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68022

Other (OTH) AF: 0.00284 AC: 6 AN: 2112

Alfa AF: 0.00113 Hom.: 2

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.4
Mutation Taster		=83/17	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs531281193; hg19: chr16-19079000; COSMIC: COSV58581334; COSMIC: COSV58581334;