rs28680987

Variant names:

• chr17-14069497-G-A
• rs28680987
• ENST00000429152.6:c.-109G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-14069497-G-A
• chr17-14069497-G-C
• chr17-14069497-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000429152.6(COX10):​c.-109G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 1,350,670 control chromosomes in the GnomAD database, including 22,099 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1929 hom., cov: 32)
  • Exomes 𝑓: 0.18 (20170 hom.)
• Consequence: COX10 ENST00000429152.6 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -3.55
• Publications: 5 publications found

Genes affected

COX10 (HGNC:2260): (cytochrome c oxidase assembly factor heme A:farnesyltransferase COX10) Cytochrome c oxidase (COX), the terminal component of the mitochondrial respiratory chain, catalyzes the electron transfer from reduced cytochrome c to oxygen. This component is a heteromeric complex consisting of 3 catalytic subunits encoded by mitochondrial genes and multiple structural subunits encoded by nuclear genes. The mitochondrially-encoded subunits function in electron transfer, and the nuclear-encoded subunits may function in the regulation and assembly of the complex. This nuclear gene encodes heme A:farnesyltransferase, which is not a structural subunit but required for the expression of functional COX and functions in the maturation of the heme A prosthetic group of COX. This protein is predicted to contain 7-9 transmembrane domains localized in the mitochondrial inner membrane. A gene mutation, which results in the substitution of a lysine for an asparagine (N204K), is identified to be responsible for cytochrome c oxidase deficiency. In addition, this gene is disrupted in patients with CMT1A (Charcot-Marie-Tooth type 1A) duplication and with HNPP (hereditary neuropathy with liability to pressure palsies) deletion. [provided by RefSeq, Jul 2008]

COX10-DT (HGNC:38873): (COX10 divergent transcript)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 17-14069497-G-A is Benign according to our data. Variant chr17-14069497-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 321804.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000429152.6. 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
	COX10	NM_001303.4	MANE Select	c.-109G>A		upstream_gene	N/A	NP_001294.2
	COX10-DT	NR_049718.1		n.-39C>T		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COX10	ENST00000429152.6	TSL:2	c.-109G>A		5_prime_UTR	Exon 1 of 3	ENSP00000397750.2	H7C101
	COX10	ENST00000664217.1		n.-109G>A		non_coding_transcript_exon	Exon 1 of 14	ENSP00000499396.1	Q12887-1
	COX10	ENST00000670279.1		n.-109G>A		non_coding_transcript_exon	Exon 1 of 11	ENSP00000499450.1	A0A590UJJ5

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23077 AN: 152082 Hom.: 1928 Cov.: 32

Gnomad AFR AF: 0.0925

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.163

GnomAD4 exome AF: 0.179 AC: 214310 AN: 1198470 Hom.: 20170 Cov.: 16 AF XY: 0.178 AC XY: 107554 AN XY: 603838

African (AFR) AF: 0.0883 AC: 2477 AN: 28044

American (AMR) AF: 0.133 AC: 5202 AN: 39008

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 2956 AN: 23826

East Asian (EAS) AF: 0.0896 AC: 3260 AN: 36372

South Asian (SAS) AF: 0.156 AC: 12026 AN: 77088

European-Finnish (FIN) AF: 0.189 AC: 9335 AN: 49316

Middle Eastern (MID) AF: 0.136 AC: 532 AN: 3918

European-Non Finnish (NFE) AF: 0.191 AC: 169913 AN: 889640

Other (OTH) AF: 0.168 AC: 8609 AN: 51258

GnomAD4 genome AF: 0.152 AC: 23086 AN: 152200 Hom.: 1929 Cov.: 32 AF XY: 0.153 AC XY: 11383 AN XY: 74412

African (AFR) AF: 0.0923 AC: 3837 AN: 41552

American (AMR) AF: 0.144 AC: 2208 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 405 AN: 3470

East Asian (EAS) AF: 0.111 AC: 572 AN: 5158

South Asian (SAS) AF: 0.152 AC: 733 AN: 4818

European-Finnish (FIN) AF: 0.191 AC: 2028 AN: 10604

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.188 AC: 12778 AN: 67986

Other (OTH) AF: 0.164 AC: 346 AN: 2114

Alfa AF: 0.169 Hom.: 283

Bravo AF: 0.147

Asia WGS AF: 0.132 AC: 459 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Leigh syndrome (1)
-	-	1	Mitochondrial complex IV deficiency, nuclear type 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.062
DANN	Benign	0.81
PhyloP100		-3.6
PromoterAI		0.22	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs28680987; hg19: chr17-13972814;