Genetic Variant COA6:p.Ser16Asn (chr1-234373513-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001206641.3(COA6):c.47G>A(p.Ser16Asn) variant causes a missense 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. 14/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S16T) has been classified as Benign.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

COA6
NM_001206641.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.43

Publications

30 publications found

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:

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

COA6-AS1 links:

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ACMG classification

Classification was made for transcript

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 (MetaRNN=0.044051945).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COA6	NM_001206641.3	MANE Select	c.47G>A	p.Ser16Asn	missense	Exon 1 of 3	NP_001193570.2	Q5JTJ3-2
COA6-AS1	NR_125961.1		n.81C>T		non_coding_transcript_exon	Exon 1 of 2
COA6	NM_001012985.2		c.-206G>A		upstream_gene	N/A	NP_001013003.1	Q5JTJ3-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COA6	ENST00000366615.10	TSL:1 MANE Select	c.47G>A	p.Ser16Asn	missense	Exon 1 of 3	ENSP00000355574.5	Q5JTJ3-2
COA6	ENST00000619305.1	TSL:1	c.-182G>A		5_prime_UTR	Exon 1 of 3	ENSP00000479686.1	Q5JTJ3-3
COA6-AS1	ENST00000451795.4	TSL:5	n.177C>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1453272

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722362

African (AFR)

AF:

0.00

AC:

AN:

33282

American (AMR)

AF:

0.00

AC:

AN:

43314

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25904

East Asian (EAS)

AF:

0.00

AC:

AN:

39506

South Asian (SAS)

AF:

0.00

AC:

AN:

85860

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52010

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1107730

Other (OTH)

AF:

0.00

AC:

AN:

59922

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.32

(source)

DANN

Benign

0.88

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0015

LIST_S2

Benign

0.20

M_CAP

Benign

0.0010

MetaRNN

Benign

0.044

MetaSVM

Benign

-0.98

PhyloP100

-3.4

PROVEAN

Benign

-0.10

REVEL

Benign

0.034

Sift

Benign

1.0

Sift4G

Benign

0.62

Vest4

0.056

MutPred

0.32

Loss of phosphorylation at S16 (P = 0.0113)

MVP

0.26

ClinPred

0.049

GERP RS

-4.4

PromoterAI

-0.42

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

gMVP

0.020

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over