17-63601153-G-A

Variant names:

• chr17-63601153-G-A
• rs1238337428
• NM_016360.4:c.70G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016360.4(TACO1):​c.70G>A​(p.Val24Ile) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TACO1 NM_016360.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.385

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]

ENSG00000288894 (HGNC:):

ACMG classification

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=0.055279493).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TACO1	NM_016360.4	c.70G>A	p.Val24Ile	missense_variant	Exon 1 of 5	ENST00000258975.7	NP_057444.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TACO1	ENST00000258975.7	c.70G>A	p.Val24Ile	missense_variant	Exon 1 of 5	1	NM_016360.4	ENSP00000258975.6
ENSG00000288894	ENST00000690765.1	n.*107-3381G>A		intron_variant	Intron 8 of 11			ENSP00000510085.1
TACO1	ENST00000684587.1	c.70G>A	p.Val24Ile	missense_variant	Exon 1 of 5			ENSP00000507435.1
TACO1	ENST00000581120.1	n.272G>A		non_coding_transcript_exon_variant	Exon 1 of 4	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Mar 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.70G>A (p.V24I) alteration is located in exon 1 (coding exon 1) of the TACO1 gene. This alteration results from a G to A substitution at nucleotide position 70, causing the valine (V) at amino acid position 24 to be replaced by an isoleucine (I). 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	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	1.5
DANN	Benign	0.93
DEOGEN2	Benign	0.18	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.094	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.46	N
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.022
Sift	Benign	0.24	T
Sift4G	Benign	0.47	T
Polyphen		0.0040	B
Vest4		0.077
MutPred		0.17		Loss of methylation at R25 (P = 0.0461);
MVP		0.030
MPC		0.33
ClinPred		0.10	T
GERP RS		-1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.039
gMVP		0.076

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

Other links and lift over

dbSNP: rs1238337428; hg19: chr17-61678512;