Variant 2-98600749-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The NM_001008215.3(COA5):c.*3C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000382 in 1,609,256 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00035 ( 1 hom. )

Consequence

COA5
NM_001008215.3 3_prime_UTR

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: -0.0840

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 Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 2-98600749-G-C is Benign according to our data. Variant chr2-98600749-G-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 281746.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COA5	NM_001008215.3 linkuse as main transcript	c.*3C>G		3_prime_UTR_variant	3/3	ENST00000328709.8	NP_001008216.1	Q86WW8

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
COA5	ENST00000328709.8 linkuse as main transcript	c.*3C>G	3_prime_UTR_variant	3/3	1	NM_001008215.3	ENSP00000330730.3	Q86WW8
COA5	ENST00000466848.1 linkuse as main transcript	n.205C>G	non_coding_transcript_exon_variant	3/3	3
COA5	ENST00000480666.1 linkuse as main transcript	n.728C>G	non_coding_transcript_exon_variant	2/2	2
COA5	ENST00000483527.5 linkuse as main transcript	n.374C>G	non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.000657

AC:

100

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.0538

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.000412

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000376

AC:

AN:

247638

Hom.:

AF XY:

0.000389

AC XY:

AN XY:

133848

show subpopulations

Gnomad AFR exome

AF:

0.0000625

Gnomad AMR exome

AF:

0.000874

Gnomad ASJ exome

AF:

0.000100

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000231

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000431

Gnomad OTH exome

AF:

0.000991

GnomAD4 exome

AF:

0.000353

AC:

515

AN:

1456962

Hom.:

Cov.:

AF XY:

0.000357

AC XY:

259

AN XY:

724832

show subpopulations

Gnomad4 AFR exome

AF:

0.000779

Gnomad4 AMR exome

AF:

0.000874

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000268

Gnomad4 FIN exome

AF:

0.0000189

Gnomad4 NFE exome

AF:

0.000257

Gnomad4 OTH exome

AF:

0.000947

GnomAD4 genome

AF:

0.000657

AC:

100

AN:

152294

Hom.:

Cov.:

AF XY:

0.000578

AC XY:

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000412

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000558

Hom.:

Bravo

AF:

0.000960

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:2

Likely benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Jul 31, 2017	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 08, 2015	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

5.7

DANN

Benign

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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