1-234373456-A-T

Variant names:

• chr1-234373456-A-T
• rs752090061
• NM_001206641.3:c.-11A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001206641.3(COA6):​c.-11A>T 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 0.00000223 in 1,346,058 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: COA6 NM_001206641.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.72
• Publications: 0 publications found

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]

COA6-AS1 (HGNC:40825): (COA6 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001206641.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COA6	NM_001206641.3	MANE Select	c.-11A>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	NP_001193570.2	Q5JTJ3-2
	COA6	NM_001206641.3	MANE Select	c.-11A>T		5_prime_UTR	Exon 1 of 3	NP_001193570.2	Q5JTJ3-2
	COA6-AS1	NR_125961.1		n.138T>A		non_coding_transcript_exon	Exon 1 of 2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COA6	ENST00000366615.10	TSL:1 MANE Select	c.-11A>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	ENSP00000355574.5	Q5JTJ3-2
	COA6	ENST00000366615.10	TSL:1 MANE Select	c.-11A>T		5_prime_UTR	Exon 1 of 3	ENSP00000355574.5	Q5JTJ3-2
	COA6-AS1	ENST00000451795.4	TSL:5	n.234T>A		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 112280 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000223 AC: 3 AN: 1346058 Hom.: 0 Cov.: 29 AF XY: 0.00000152 AC XY: 1 AN XY: 659476

African (AFR) AF: 0.00 AC: 0 AN: 29550

American (AMR) AF: 0.00 AC: 0 AN: 25846

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21158

East Asian (EAS) AF: 0.00 AC: 0 AN: 35438

South Asian (SAS) AF: 0.00 AC: 0 AN: 72228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46570

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5404

European-Non Finnish (NFE) AF: 0.00000285 AC: 3 AN: 1054330

Other (OTH) AF: 0.00 AC: 0 AN: 55534

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.65
DANN	Benign	0.39
PhyloP100		-2.7
PromoterAI		0.0068	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs752090061; hg19: chr1-234509202;