2-98608476-G-A

Position:

• chr2-98608476-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001008215.3(COA5):​c.-71C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00147 in 1,226,632 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0065 (18 hom., cov: 33)
  • Exomes 𝑓: 0.00076 (5 hom.)
• Consequence: COA5 NM_001008215.3 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.353

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=-0.81).
• BP6: Variant 2-98608476-G-A is Benign according to our data. Variant chr2-98608476-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1317510.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00648 (988/152372) while in subpopulation AFR AF= 0.0222 (925/41590). AF 95% confidence interval is 0.0211. There are 18 homozygotes in gnomad4. There are 464 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COA5	NM_001008215.3	c.-71C>T		5_prime_UTR_variant	1/3	ENST00000328709.8	NP_001008216.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COA5	ENST00000328709.8	c.-71C>T		5_prime_UTR_variant	1/3	1	NM_001008215.3	ENSP00000330730.3
COA5	ENST00000409997.1	c.-71C>T		5_prime_UTR_variant	1/3	4		ENSP00000386934.1
COA5	ENST00000483527.5	n.32C>T		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes AF: 0.00649 AC: 988 AN: 152254 Hom.: 18 Cov.: 33

Gnomad AFR AF: 0.0223

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000413

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00527

GnomAD4 exome AF: 0.000757 AC: 813 AN: 1074260 Hom.: 5 Cov.: 14 AF XY: 0.000675 AC XY: 367 AN XY: 543850

Gnomad4 AFR exome AF: 0.0224

Gnomad4 AMR exome AF: 0.00161

Gnomad4 ASJ exome AF: 0.000820

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000109

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000479

Gnomad4 OTH exome AF: 0.00208

GnomAD4 genome AF: 0.00648 AC: 988 AN: 152372 Hom.: 18 Cov.: 33 AF XY: 0.00623 AC XY: 464 AN XY: 74518

Gnomad4 AFR AF: 0.0222

Gnomad4 AMR AF: 0.00216

Gnomad4 ASJ AF: 0.00230

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00521

Alfa AF: 0.00119 Hom.: 0

Bravo AF: 0.00742

Asia WGS AF: 0.00115 AC: 4 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 03, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.5
DANN	Benign	0.84
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

Other links and lift over

dbSNP: rs192282513; hg19: chr2-99224939;