Genetic Variant NM_016360.4:c.112G>A (chr17-63601195-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016360.4(TACO1):c.112G>A(p.Glu38Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000043 in 1,395,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000043 ( 0 hom. )

Consequence

TACO1
NM_016360.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0780

Publications

0 publications found

Variant links:

Genes affected

TACO1 (HGNC:24316): (translational activator of cytochrome c oxidase I) This gene encodes a mitochondrial protein that function as a translational activator of mitochondrially-encoded cytochrome c oxidase 1. Mutations in this gene are associated with Leigh syndrome.[provided by RefSeq, Mar 2010]

TACO1 Gene-Disease associations (from GenCC):

mitochondrial disease
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
mitochondrial complex IV deficiency, nuclear type 8
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P
Leigh syndrome
Inheritance: AR Classification: MODERATE Submitted by: ClinGen
Leigh syndrome with leukodystrophy
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

TACO1 links:

ENSG00000288894 (HGNC:):

ENSG00000288894 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07729152).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016360.4. 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
	TACO1	NM_016360.4	MANE Select	c.112G>A	p.Glu38Lys	missense	Exon 1 of 5	NP_057444.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TACO1	ENST00000258975.7	TSL:1 MANE Select	c.112G>A	p.Glu38Lys	missense	Exon 1 of 5	ENSP00000258975.6	Q9BSH4
ENSG00000288894	ENST00000690765.1		n.*107-3339G>A		intron	N/A	ENSP00000510085.1
TACO1	ENST00000684587.1		c.112G>A	p.Glu38Lys	missense	Exon 1 of 5	ENSP00000507435.1	A0A804HJB7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000430

AC:

AN:

1395870

Hom.:

Cov.:

AF XY:

0.00000290

AC XY:

AN XY:

689810

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31890

American (AMR)

AF:

0.0000273

AC:

AN:

36598

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24746

East Asian (EAS)

AF:

0.00

AC:

AN:

36010

South Asian (SAS)

AF:

0.00

AC:

AN:

80510

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45748

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4622

European-Non Finnish (NFE)

AF:

0.00000464

AC:

AN:

1078300

Other (OTH)

AF:

0.00

AC:

AN:

57446

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Mitochondrial complex IV deficiency, nuclear type 8 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

7.6

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.21

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.45

M_CAP

Benign

0.0060

MetaRNN

Benign

0.077

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.97

PhyloP100

-0.078

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.10

REVEL

Benign

0.042

Sift

Pathogenic

0.0

Sift4G

Benign

0.42

Polyphen

0.0040

Vest4

0.12

MutPred

0.18

Gain of methylation at E38 (P = 0.0071)

MVP

0.014

MPC

0.46

ClinPred

0.22

GERP RS

2.9

PromoterAI

-0.078

Neutral

(source)

Varity_R

0.086

gMVP

0.25

Mutation Taster

=93/7

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over