rs1029687

Variant names:

• chr17-14127335-T-A
• rs1029687
• NM_001303.4:c.624+25093T>A

Your query was ambiguous. Multiple possible variants found:

• chr17-14127335-T-A
• chr17-14127335-T-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001303.4(COX10):​c.624+25093T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 152,002 control chromosomes in the GnomAD database, including 18,612 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.49 (18612 hom., cov: 33)
• Consequence: COX10 NM_001303.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.398
• Publications: 2 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 Gene-Disease associations (from GenCC):

• mitochondrial complex IV deficiency, nuclear type 3

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Leigh syndrome

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen
• cytochrome-c oxidase deficiency disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COX10	NM_001303.4	c.624+25093T>A		intron_variant	Intron 4 of 6	ENST00000261643.8	NP_001294.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COX10	ENST00000261643.8	c.624+25093T>A		intron_variant	Intron 4 of 6	1	NM_001303.4	ENSP00000261643.3

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74808 AN: 151884 Hom.: 18610 Cov.: 33

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.375

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.531

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.500

Gnomad OTH AF: 0.460

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.492 AC: 74841 AN: 152002 Hom.: 18612 Cov.: 33 AF XY: 0.492 AC XY: 36587 AN XY: 74310

African (AFR) AF: 0.487 AC: 20185 AN: 41474

American (AMR) AF: 0.523 AC: 7989 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.375 AC: 1299 AN: 3462

East Asian (EAS) AF: 0.460 AC: 2377 AN: 5168

South Asian (SAS) AF: 0.532 AC: 2564 AN: 4822

European-Finnish (FIN) AF: 0.474 AC: 5005 AN: 10570

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.500 AC: 33926 AN: 67908

Other (OTH) AF: 0.454 AC: 960 AN: 2114

Alfa AF: 0.498 Hom.: 2301

Bravo AF: 0.491

Asia WGS AF: 0.453 AC: 1561 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.42
DANN	Benign	0.49
PhyloP100		-0.40
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1029687; hg19: chr17-14030652;