ENST00000366612.1:c.-405G>A

Variant names:

• chr1-234373841-G-A
• rs947861426
• ENST00000366612.1:c.-405G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 4P and 1B. PM2 PP5_Moderate BP4

The ENST00000366612.1(COA6):​c.-405G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: COA6 ENST00000366612.1 5_prime_UTR
• Scores: Splicing: ADA: 0.9999
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: -0.155
• 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: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 1-234373841-G-A is Pathogenic according to our data. Variant chr1-234373841-G-A is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 1690965.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP4: Computational evidence support a benign effect (BayesDel_addAF=-0.39789). . Strength limited to SUPPORTING due to the PP5.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000366612.1. 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.212+163G>A		intron	N/A	NP_001193570.2	Q5JTJ3-2
	COA6	NM_001301733.1		c.-405G>A		5_prime_UTR	Exon 1 of 2	NP_001288662.1	Q5JTJ3-3
	COA6	NM_001012985.2		c.122+1G>A		splice_donor intron	N/A	NP_001013003.1	Q5JTJ3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COA6	ENST00000366612.1	TSL:1	c.-405G>A		5_prime_UTR	Exon 1 of 2	ENSP00000355571.1	Q5JTJ3-3
	COA6	ENST00000366615.10	TSL:1 MANE Select	c.212+163G>A		intron	N/A	ENSP00000355574.5	Q5JTJ3-2
	COA6	ENST00000366613.1	TSL:1	c.122+1G>A		splice_donor intron	N/A	ENSP00000355572.1	Q5JTJ3-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	See cases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.6
DANN	Benign	0.85
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.013	N
PhyloP100		-0.15
GERP RS		-0.11
PromoterAI		-0.027	Neutral
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Benign	0.64
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs947861426; hg19: chr1-234509587;