rs1447369735

Variant names:

• chr17-63601136-T-A
• NM_016360.4:c.53T>A

Your query was ambiguous. Multiple possible variants found:

• chr17-63601136-T-A
• chr17-63601136-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016360.4(TACO1):​c.53T>A​(p.Leu18Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000719 in 1,391,162 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L18P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: TACO1 NM_016360.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08078897).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TACO1	NM_016360.4	c.53T>A	p.Leu18Gln	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.53T>A	p.Leu18Gln	missense_variant	Exon 1 of 5	1	NM_016360.4	ENSP00000258975.6
ENSG00000288894	ENST00000690765.1	n.*107-3398T>A		intron_variant	Intron 8 of 11			ENSP00000510085.1
TACO1	ENST00000684587.1	c.53T>A	p.Leu18Gln	missense_variant	Exon 1 of 5			ENSP00000507435.1
TACO1	ENST00000581120.1	n.255T>A		non_coding_transcript_exon_variant	Exon 1 of 4	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.19e-7 AC: 1 AN: 1391162 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 685962

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: 9.28e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	16
DANN	Benign	0.64
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PrimateAI	Benign	0.48	T
PROVEAN	Benign	0.010	N
REVEL	Benign	0.12
Sift	Benign	0.28	T
Sift4G	Benign	0.26	T
Polyphen		0.089	B
Vest4		0.16
MutPred		0.23		Gain of solvent accessibility (P = 0.0137);
MVP		0.099
MPC		0.43
ClinPred		0.17	T
GERP RS		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.084
gMVP		0.17

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-61678495;