2-98604430-T-C

Position:

• chr2-98604430-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001008215.3(COA5):​c.100-239A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00798 in 497,100 control chromosomes in the GnomAD database, including 137 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (114 hom., cov: 33)
  • Exomes 𝑓: 0.0028 (23 hom.)
• Consequence: COA5 NM_001008215.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.976

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 2-98604430-T-C is Benign according to our data. Variant chr2-98604430-T-C is described in ClinVar as [Benign]. Clinvar id is 1290683.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0662 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COA5	NM_001008215.3	c.100-239A>G		intron_variant		ENST00000328709.8	NP_001008216.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COA5	ENST00000328709.8	c.100-239A>G		intron_variant		1	NM_001008215.3	ENSP00000330730.3

Frequencies

GnomAD3 genomes AF: 0.0196 AC: 2976 AN: 152220 Hom.: 110 Cov.: 33

Gnomad AFR AF: 0.0679

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00706

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.0129

GnomAD4 exome AF: 0.00281 AC: 968 AN: 344762 Hom.: 23 Cov.: 0 AF XY: 0.00225 AC XY: 414 AN XY: 184182

Gnomad4 AFR exome AF: 0.0676

Gnomad4 AMR exome AF: 0.00656

Gnomad4 ASJ exome AF: 0.00105

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000233

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000148

Gnomad4 OTH exome AF: 0.00689

GnomAD4 genome AF: 0.0197 AC: 2999 AN: 152338 Hom.: 114 Cov.: 33 AF XY: 0.0194 AC XY: 1444 AN XY: 74504

Gnomad4 AFR AF: 0.0683

Gnomad4 AMR AF: 0.00705

Gnomad4 ASJ AF: 0.00230

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000250

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.0150 Hom.: 3

Bravo AF: 0.0225

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 15, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.31
DANN	Benign	0.49

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

Other links and lift over

dbSNP: rs17034163; hg19: chr2-99220893;