rs7211577

Positions:

• chr17-14210963-G-A
• chr17-14210963-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000664217.1(COX10):​c.*837-325G>A variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 151,904 control chromosomes in the GnomAD database, including 18,870 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 (18870 hom., cov: 31)
• Consequence: COX10 ENST00000664217.1 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.115

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COX10	ENST00000458492.1	n.79-325G>A		intron_variant, non_coding_transcript_variant		1
COX10	ENST00000664217.1	c.*837-325G>A		intron_variant, NMD_transcript_variant				ENSP00000499396
COX10	ENST00000670279.1	c.*536-325G>A		intron_variant, NMD_transcript_variant				ENSP00000499450

Frequencies

GnomAD3 genomes AF: 0.494 AC: 74969 AN: 151786 Hom.: 18879 Cov.: 31

Gnomad AFR AF: 0.466

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.541

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.509

Gnomad OTH AF: 0.505

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

GnomAD4 genome AF: 0.494 AC: 74979 AN: 151904 Hom.: 18870 Cov.: 31 AF XY: 0.495 AC XY: 36755 AN XY: 74254

Gnomad4 AFR AF: 0.465

Gnomad4 AMR AF: 0.389

Gnomad4 ASJ AF: 0.476

Gnomad4 EAS AF: 0.541

Gnomad4 SAS AF: 0.619

Gnomad4 FIN AF: 0.569

Gnomad4 NFE AF: 0.508

Gnomad4 OTH AF: 0.505

Alfa AF: 0.509 Hom.: 10563

Bravo AF: 0.477

Asia WGS AF: 0.536 AC: 1866 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.33

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7211577; hg19: chr17-14114280; COSMIC: COSV55403776;