1-244835910-T-TC

Position:

• chr1-244835910-T-TC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_198076.6(COX20):​c.42+156dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0256 in 152,238 control chromosomes in the GnomAD database, including 76 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.026 (76 hom., cov: 32)
• Consequence: COX20 NM_198076.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.577

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 -10 ACMG points.

• BP6: Variant 1-244835910-T-TC is Benign according to our data. Variant chr1-244835910-T-TC is described in ClinVar as [Likely_benign]. Clinvar id is 1704931.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0256 (3898/152238) while in subpopulation NFE AF= 0.0394 (2681/67996). AF 95% confidence interval is 0.0382. There are 76 homozygotes in gnomad4. There are 1819 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 76 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COX20	NM_198076.6	c.42+156dup		intron_variant		ENST00000411948.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COX20	ENST00000411948.7	c.42+156dup		intron_variant		1	NM_198076.6	P1
COX20	ENST00000391839.6	n.101+156dup		intron_variant, non_coding_transcript_variant		1
COX20	ENST00000366528.3	c.42+156dup		intron_variant		2
COX20	ENST00000498262.1	n.98+156dup		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0256 AC: 3901 AN: 152120 Hom.: 75 Cov.: 32

Gnomad AFR AF: 0.00734

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.0145

Gnomad ASJ AF: 0.0346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0364

Gnomad FIN AF: 0.0239

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0394

Gnomad OTH AF: 0.0254

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

GnomAD4 genome AF: 0.0256 AC: 3898 AN: 152238 Hom.: 76 Cov.: 32 AF XY: 0.0244 AC XY: 1819 AN XY: 74446

Gnomad4 AFR AF: 0.00731

Gnomad4 AMR AF: 0.0145

Gnomad4 ASJ AF: 0.0346

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0361

Gnomad4 FIN AF: 0.0239

Gnomad4 NFE AF: 0.0394

Gnomad4 OTH AF: 0.0251

Alfa AF: 0.0334 Hom.: 12

Bravo AF: 0.0235

Asia WGS AF: 0.00924 AC: 33 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 10, 2020

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs142283268; hg19: chr1-244999212;