Variant 2-98608380-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong

The NM_001008215.3(COA5):c.26C>T(p.Pro9Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000288 in 1,605,364 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00028 ( 0 hom. )

Consequence

COA5
NM_001008215.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts U:1B:2

Conservation

PhyloP100: 3.19

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 -10 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.006760329).

BP6

Variant 2-98608380-G-A is Benign according to our data. Variant chr2-98608380-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 559351.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COA5	NM_001008215.3 linkuse as main transcript	c.26C>T	p.Pro9Leu	missense_variant	1/3	ENST00000328709.8	NP_001008216.1	Q86WW8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
COA5	ENST00000328709.8 linkuse as main transcript	c.26C>T	p.Pro9Leu	missense_variant	1/3	1	NM_001008215.3	ENSP00000330730.3	Q86WW8
COA5	ENST00000409997.1 linkuse as main transcript	c.26C>T	p.Pro9Leu	missense_variant	1/3	4		ENSP00000386934.1	B9A057
COA5	ENST00000483527.5 linkuse as main transcript	n.128C>T		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes

AF:

0.000328

AC:

AN:

152258

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000367

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000394

AC:

AN:

230842

Hom.:

AF XY:

0.000420

AC XY:

AN XY:

126334

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000151

Gnomad ASJ exome

AF:

0.00602

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000250

Gnomad OTH exome

AF:

0.000351

GnomAD4 exome

AF:

0.000284

AC:

412

AN:

1452988

Hom.:

Cov.:

AF XY:

0.000298

AC XY:

215

AN XY:

722378

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.000296

Gnomad4 ASJ exome

AF:

0.00428

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000236

Gnomad4 OTH exome

AF:

0.000350

GnomAD4 genome

AF:

0.000328

AC:

AN:

152376

Hom.:

Cov.:

AF XY:

0.000295

AC XY:

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00519

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000367

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000522

Hom.:

Bravo

AF:

0.000302

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000583

AC:

ExAC

AF:

0.000265

AC:

ClinVar

Significance: Likely benign

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:2

Uncertain significance, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Mar 14, 2016	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Sep 26, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.023

T;T

Eigen

Benign

-0.082

Eigen_PC

Benign

0.063

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.75

T;T

M_CAP

Benign

0.065

MetaRNN

Benign

0.0068

T;T

MetaSVM

Benign

-0.71

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.63

N;N

REVEL

Benign

0.18

Sift

Benign

0.28

T;T

Sift4G

Benign

0.26

T;T

Polyphen

0.0080

B;.

Vest4

0.39

MVP

0.44

MPC

0.21

ClinPred

0.16

GERP RS

5.2

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.7

Varity_R

0.13

gMVP

0.28

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