rs770522096

Variant names:

• chr1-244841927-CT-C
• rs770522096
• NM_198076.6:c.43-9delT

Your query was ambiguous. Multiple possible variants found:

• chr1-244841927-CT-C
• chr1-244841927-CT-CTT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_198076.6(COX20):​c.43-9delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000268 in 1,308,182 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000027 (0 hom.)
• Consequence: COX20 NM_198076.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.164

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]

HNRNPU (HGNC:5048): (heterogeneous nuclear ribonucleoprotein U) This gene encodes a member of a family of proteins that bind nucleic acids and function in the formation of ribonucleoprotein complexes in the nucleus with heterogeneous nuclear RNA (hnRNA). The encoded protein has affinity for both RNA and DNA, and binds scaffold-attached region (SAR) DNA. Mutations in this gene have been associated with epileptic encephalopathy, early infantile, 54. A pseudogene of this gene has been identified on chromosome 14. [provided by RefSeq, Jun 2017]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COX20	NM_198076.6	c.43-9delT		intron_variant	Intron 1 of 3	ENST00000411948.7	NP_932342.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COX20	ENST00000411948.7	c.43-9delT		intron_variant	Intron 1 of 3	1	NM_198076.6	ENSP00000406327.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000268 AC: 35 AN: 1308182 Hom.: 0 Cov.: 21 AF XY: 0.0000304 AC XY: 20 AN XY: 657466

Gnomad4 AFR exome AF: 0.0000347

Gnomad4 AMR exome AF: 0.0000280

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000257

Gnomad4 SAS exome AF: 0.000127

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000212

Gnomad4 OTH exome AF: 0.0000182

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs770522096; hg19: chr1-245005229;