Variant chr1-244841783-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_198076.6(COX20):c.43-161G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 570,148 control chromosomes in the GnomAD database, including 5,769 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.14 ( 1578 hom., cov: 32)

Exomes 𝑓: 0.13 ( 4191 hom. )

Consequence

COX20
NM_198076.6 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.336

Variant links:

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]

COX20 links:

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]

HNRNPU links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 1-244841783-G-C is Benign according to our data. Variant chr1-244841783-G-C is described in ClinVar as [Benign]. Clinvar id is 683598.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COX20	NM_198076.6 linkuse as main transcript	c.43-161G>C		intron_variant		ENST00000411948.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COX20	ENST00000411948.7 linkuse as main transcript	c.43-161G>C		intron_variant		1	NM_198076.6	P1	Q5RI15-1

Frequencies

GnomAD3 genomes

AF:

0.138

AC:

21022

AN:

152032

Hom.:

1578

Cov.:

show subpopulations

Gnomad AFR

AF:

0.155

Gnomad AMI

AF:

0.170

Gnomad AMR

AF:

0.118

Gnomad ASJ

AF:

0.253

Gnomad EAS

AF:

0.0119

Gnomad SAS

AF:

0.126

Gnomad FIN

AF:

0.0913

Gnomad MID

AF:

0.313

Gnomad NFE

AF:

0.143

Gnomad OTH

AF:

0.169

GnomAD4 exome

AF:

0.131

AC:

54767

AN:

417998

Hom.:

4191

Cov.:

AF XY:

0.132

AC XY:

28986

AN XY:

220074

show subpopulations

Gnomad4 AFR exome

AF:

0.151

Gnomad4 AMR exome

AF:

0.104

Gnomad4 ASJ exome

AF:

0.247

Gnomad4 EAS exome

AF:

0.00596

Gnomad4 SAS exome

AF:

0.136

Gnomad4 FIN exome

AF:

0.0971

Gnomad4 NFE exome

AF:

0.143

Gnomad4 OTH exome

AF:

0.146

GnomAD4 genome

AF:

0.138

AC:

21017

AN:

152150

Hom.:

1578

Cov.:

AF XY:

0.137

AC XY:

10211

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.154

Gnomad4 AMR

AF:

0.118

Gnomad4 ASJ

AF:

0.253

Gnomad4 EAS

AF:

0.0118

Gnomad4 SAS

AF:

0.126

Gnomad4 FIN

AF:

0.0913

Gnomad4 NFE

AF:

0.142

Gnomad4 OTH

AF:

0.167

Alfa

AF:

0.0592

Hom.:

Bravo

AF:

0.140

Asia WGS

AF:

0.0700

AC:

246

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

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

-0.90

CADD

Benign

2.3

DANN

Benign

0.35

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over