Variant chr1-234373726-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001206641.3(COA6):c.212+48C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,538 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

COA6
NM_001206641.3 intron

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.899

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06443241).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COA6	NM_001206641.3 linkuse as main transcript	c.212+48C>T		intron_variant		ENST00000366615.10	NP_001193570.2	Q5JTJ3-2
COA6	NM_001301733.1 linkuse as main transcript	c.-520C>T		5_prime_UTR_premature_start_codon_gain_variant	1/2		NP_001288662.1	Q5JTJ3-3
COA6	NM_001012985.2 linkuse as main transcript	c.8C>T	p.Pro3Leu	missense_variant	1/3		NP_001013003.1	Q5JTJ3-1
COA6	NM_001301733.1 linkuse as main transcript	c.-520C>T		5_prime_UTR_variant	1/2		NP_001288662.1	Q5JTJ3-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COA6	ENST00000366615.10 linkuse as main transcript	c.212+48C>T		intron_variant		1	NM_001206641.3	ENSP00000355574.5		Q5JTJ3-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461538

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727052

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 24, 2022

The c.8C>T (p.P3L) alteration is located in exon 1 (coding exon 1) of the COA6 gene. This alteration results from a C to T substitution at nucleotide position 8, causing the proline (P) at amino acid position 3 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.52

CADD

Benign

5.1

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0040

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.43

M_CAP

Benign

0.0053

MetaRNN

Benign

0.064

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.57

REVEL

Benign

0.071

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.0020

Vest4

0.21

MutPred

0.17

Loss of glycosylation at P3 (P = 0.0337);

MVP

0.22

MPC

0.45

ClinPred

0.43

GERP RS

0.66

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.073

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over