1-244835765-G-A

Position:

• chr1-244835765-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_198076.6(COX20):​c.42+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0208 in 1,255,116 control chromosomes in the GnomAD database, including 307 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (37 hom., cov: 32)
  • Exomes 𝑓: 0.021 (270 hom.)
• Consequence: COX20 NM_198076.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.16

Genes affected

COX20 (HGNC:26970): (cytochrome c oxidase assembly factor COX20) This gene encodes a protein that plays a role in the assembly of cytochrome C oxidase, an important component of the respiratory pathway. It contains two transmembrane helices and localizes to the mitochondrial membrane. Mutations in this gene can cause mitochondrial complex IV deficiency, which results in ataxia and muscle hypotonia. There are multiple pseudogenes for this gene. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2015]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 1-244835765-G-A is Benign according to our data. Variant chr1-244835765-G-A is described in ClinVar as [Benign]. Clinvar id is 137020.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.022 (3351/152164) while in subpopulation NFE AF= 0.0254 (1726/67956). AF 95% confidence interval is 0.0244. There are 37 homozygotes in gnomad4. There are 1585 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 37 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COX20	NM_198076.6	c.42+9G>A		intron_variant		ENST00000411948.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COX20	ENST00000411948.7	c.42+9G>A		intron_variant		1	NM_198076.6	P1
COX20	ENST00000391839.6	n.101+9G>A		intron_variant, non_coding_transcript_variant		1
COX20	ENST00000366528.3	c.42+9G>A		intron_variant		2
COX20	ENST00000498262.1	n.98+9G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0220 AC: 3341 AN: 152046 Hom.: 36 Cov.: 32

Gnomad AFR AF: 0.0210

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0249

Gnomad ASJ AF: 0.0262

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.0161

Gnomad FIN AF: 0.00961

Gnomad MID AF: 0.0255

Gnomad NFE AF: 0.0254

Gnomad OTH AF: 0.0354

GnomAD3 exomes AF: 0.0275 AC: 141 AN: 5120 Hom.: 4 AF XY: 0.0273 AC XY: 87 AN XY: 3188

Gnomad AFR exome AF: 0.0211

Gnomad AMR exome AF: 0.0174

Gnomad ASJ exome AF: 0.0283

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0261

Gnomad FIN exome AF: 0.0162

Gnomad NFE exome AF: 0.0385

Gnomad OTH exome AF: 0.0738

GnomAD4 exome AF: 0.0206 AC: 22703 AN: 1102952 Hom.: 270 Cov.: 31 AF XY: 0.0207 AC XY: 10856 AN XY: 525274

Gnomad4 AFR exome AF: 0.0188

Gnomad4 AMR exome AF: 0.0204

Gnomad4 ASJ exome AF: 0.0206

Gnomad4 EAS exome AF: 0.000299

Gnomad4 SAS exome AF: 0.0149

Gnomad4 FIN exome AF: 0.0116

Gnomad4 NFE exome AF: 0.0215

Gnomad4 OTH exome AF: 0.0226

GnomAD4 genome AF: 0.0220 AC: 3351 AN: 152164 Hom.: 37 Cov.: 32 AF XY: 0.0213 AC XY: 1585 AN XY: 74394

Gnomad4 AFR AF: 0.0211

Gnomad4 AMR AF: 0.0248

Gnomad4 ASJ AF: 0.0262

Gnomad4 EAS AF: 0.000388

Gnomad4 SAS AF: 0.0164

Gnomad4 FIN AF: 0.00961

Gnomad4 NFE AF: 0.0254

Gnomad4 OTH AF: 0.0360

Alfa AF: 0.0295 Hom.: 4

Bravo AF: 0.0216

Asia WGS AF: 0.0180 AC: 61 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Feb 22, 2016	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 28, 2013

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.7
DANN	Benign	0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs192100928; hg19: chr1-244999067;