1-234374119-T-G

Position:

• chr1-234374119-T-G

Variant summary

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

The NM_001301733.1(COA6):​c.-127T>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 1,080,914 control chromosomes in the GnomAD database, including 83,810 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.49 (18627 hom., cov: 29)
  • Exomes 𝑓: 0.39 (65183 hom.)
• Consequence: COA6 NM_001301733.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.308

Genes affected

COA6 (HGNC:18025): (cytochrome c oxidase assembly factor 6) This gene encodes a member of the cytochrome c oxidase subunit 6B family. The encoded protein associates with cytochrome c oxidase may act has an cytochrome c oxidase mitochondrial respiratory complex VI assembly factor. Mutations in this gene may be associated with fatal infantile cardiomyopathy. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2014]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 1-234374119-T-G is Benign according to our data. Variant chr1-234374119-T-G is described in ClinVar as [Benign]. Clinvar id is 1234340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COA6	NM_001206641.3	c.213-111T>G		intron_variant		ENST00000366615.10	NP_001193570.2
COA6	NM_001301733.1	c.-127T>G		5_prime_UTR_premature_start_codon_gain_variant	1/2		NP_001288662.1
COA6	NM_001301733.1	c.-127T>G		5_prime_UTR_variant	1/2		NP_001288662.1
COA6	NM_001012985.2	c.123-111T>G		intron_variant			NP_001013003.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COA6	ENST00000366615.10	c.213-111T>G		intron_variant		1	NM_001206641.3	ENSP00000355574.5

Frequencies

GnomAD3 genomes AF: 0.485 AC: 72699 AN: 149820 Hom.: 18599 Cov.: 29

Gnomad AFR AF: 0.661

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.539

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.403

Gnomad OTH AF: 0.461

GnomAD4 exome AF: 0.391 AC: 363698 AN: 930982 Hom.: 65183 Cov.: 12 AF XY: 0.389 AC XY: 180676 AN XY: 464836

Gnomad4 AFR exome AF: 0.629

Gnomad4 AMR exome AF: 0.509

Gnomad4 ASJ exome AF: 0.367

Gnomad4 EAS exome AF: 0.372

Gnomad4 SAS exome AF: 0.354

Gnomad4 FIN exome AF: 0.371

Gnomad4 NFE exome AF: 0.385

Gnomad4 OTH exome AF: 0.399

GnomAD4 genome AF: 0.485 AC: 72770 AN: 149932 Hom.: 18627 Cov.: 29 AF XY: 0.483 AC XY: 35330 AN XY: 73148

Gnomad4 AFR AF: 0.661

Gnomad4 AMR AF: 0.539

Gnomad4 ASJ AF: 0.394

Gnomad4 EAS AF: 0.465

Gnomad4 SAS AF: 0.393

Gnomad4 FIN AF: 0.362

Gnomad4 NFE AF: 0.403

Gnomad4 OTH AF: 0.457

Alfa AF: 0.423 Hom.: 848

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 06, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.4
DANN	Benign	0.71

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: rs45577939; hg19: chr1-234509865;