Genetic Variant NM_016360.4:c.98G>C (chr17-63601181-G-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_016360.4(TACO1):c.98G>C(p.Arg33Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/22 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. R33L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TACO1
NM_016360.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.08

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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.057271153).

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.98G>C	p.Arg33Pro	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.98G>C	p.Arg33Pro	missense	Exon 1 of 5	ENSP00000258975.6	Q9BSH4
ENSG00000288894	ENST00000690765.1		n.*107-3353G>C		intron	N/A	ENSP00000510085.1
TACO1	ENST00000684587.1		c.98G>C	p.Arg33Pro	missense	Exon 1 of 5	ENSP00000507435.1	A0A804HJB7

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151982

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1397492

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

689426

African (AFR)

AF:

0.00

AC:

AN:

31820

American (AMR)

AF:

0.00

AC:

AN:

35878

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25084

East Asian (EAS)

AF:

0.00

AC:

AN:

36114

South Asian (SAS)

AF:

0.00

AC:

AN:

79632

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47150

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4374

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1079646

Other (OTH)

AF:

0.00

AC:

AN:

57794

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

152106

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74378

African (AFR)

AF:

0.00

AC:

AN:

41544

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5134

South Asian (SAS)

AF:

0.00

AC:

AN:

4794

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10586

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67970

Other (OTH)

AF:

0.00

AC:

AN:

2116

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.68

CADD

Benign

1.6

(source)

DANN

Benign

0.65

DEOGEN2

Benign

0.18

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.33

M_CAP

Benign

0.0025

MetaRNN

Benign

0.057

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

-3.1

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.26

REVEL

Benign

0.034

Sift

Benign

0.24

Sift4G

Benign

0.26

Polyphen

0.0

Vest4

0.11

MutPred

0.20

Gain of glycosylation at R33 (P = 0.0058)

MVP

0.014

MPC

0.59

ClinPred

0.087

GERP RS

-5.5

PromoterAI

-0.29

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.11

gMVP

0.17

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

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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