Variant 2-98608129-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001008215.3(COA5):c.99+178T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0169 in 622,246 control chromosomes in the GnomAD database, including 112 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.014 ( 23 hom., cov: 33)

Exomes 𝑓: 0.018 ( 89 hom. )

Consequence

COA5
NM_001008215.3 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.62

Variant links:

Genes affected

COA5 (HGNC:33848): (cytochrome c oxidase assembly factor 5) This gene encodes an ortholog of yeast Pet191, which in yeast is a subunit of a large oligomeric complex associated with the mitochondrial inner membrane, and required for the assembly of the cytochrome c oxidase complex. Mutations in this gene are associated with mitochondrial complex IV deficiency, a disorder of the mitochondrial respiratory chain with heterogeneous clinical manifestations, ranging from isolated myopathy to a severe disease affecting several tissues and organs. [provided by RefSeq, Dec 2011]

COA5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 2-98608129-A-G is Benign according to our data. Variant chr2-98608129-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1317824.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0141 (2153/152374) while in subpopulation SAS AF= 0.0271 (131/4830). AF 95% confidence interval is 0.0233. There are 23 homozygotes in gnomad4. There are 1033 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COA5	NM_001008215.3 linkuse as main transcript	c.99+178T>C		intron_variant		ENST00000328709.8	NP_001008216.1	Q86WW8

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
COA5	ENST00000328709.8 linkuse as main transcript	c.99+178T>C	intron_variant	1	NM_001008215.3	ENSP00000330730.3	Q86WW8
COA5	ENST00000409997.1 linkuse as main transcript	c.99+178T>C	intron_variant	4		ENSP00000386934.1	B9A057
COA5	ENST00000483527.5 linkuse as main transcript	n.245+134T>C	intron_variant	2

Frequencies

GnomAD3 genomes

AF:

0.0141

AC:

2154

AN:

152256

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00420

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0222

Gnomad ASJ

AF:

0.0118

Gnomad EAS

AF:

0.00193

Gnomad SAS

AF:

0.0271

Gnomad FIN

AF:

0.0125

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0191

Gnomad OTH

AF:

0.0110

GnomAD4 exome

AF:

0.0178

AC:

8370

AN:

469872

Hom.:

AF XY:

0.0184

AC XY:

4596

AN XY:

249852

show subpopulations

Gnomad4 AFR exome

AF:

0.00259

Gnomad4 AMR exome

AF:

0.0308

Gnomad4 ASJ exome

AF:

0.0128

Gnomad4 EAS exome

AF:

0.000288

Gnomad4 SAS exome

AF:

0.0264

Gnomad4 FIN exome

AF:

0.0171

Gnomad4 NFE exome

AF:

0.0183

Gnomad4 OTH exome

AF:

0.0174

GnomAD4 genome

AF:

0.0141

AC:

2153

AN:

152374

Hom.:

Cov.:

AF XY:

0.0139

AC XY:

1033

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.00418

Gnomad4 AMR

AF:

0.0221

Gnomad4 ASJ

AF:

0.0118

Gnomad4 EAS

AF:

0.00193

Gnomad4 SAS

AF:

0.0271

Gnomad4 FIN

AF:

0.0125

Gnomad4 NFE

AF:

0.0191

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.00718

Hom.:

Bravo

AF:

0.0150

Asia WGS

AF:

0.0160

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.8

DANN

Benign

0.37

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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