NM_016360.4:c.-168A>C

Variant names:

• chr17-63600916-A-C
• rs564253011
• NM_016360.4:c.-168A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016360.4(TACO1):​c.-168A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000197 in 507,924 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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)
  • Exomes 𝑓: 0.0000020 (0 hom.)
• Consequence: TACO1 NM_016360.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.03
• Publications: 0 publications found

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

ENSG00000288894 (HGNC:):

ACMG classification

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 (BayesDel_noAF=-0.96).

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.-168A>C		5_prime_UTR	Exon 1 of 5	NP_057444.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TACO1	ENST00000258975.7	TSL:1 MANE Select	c.-168A>C		5_prime_UTR	Exon 1 of 5	ENSP00000258975.6	Q9BSH4
	ENSG00000288894	ENST00000690765.1		n.*107-3618A>C		intron	N/A	ENSP00000510085.1
	TACO1	ENST00000581120.1	TSL:2	n.35A>C		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000197 AC: 1 AN: 507924 Hom.: 0 Cov.: 7 AF XY: 0.00000379 AC XY: 1 AN XY: 264056

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 11350

American (AMR) AF: 0.00 AC: 0 AN: 16962

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13476

East Asian (EAS) AF: 0.00 AC: 0 AN: 28762

South Asian (SAS) AF: 0.00 AC: 0 AN: 45132

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29662

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2082

European-Non Finnish (NFE) AF: 0.00000300 AC: 1 AN: 332918

Other (OTH) AF: 0.00 AC: 0 AN: 27580

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.34
DANN	Benign	0.37
PhyloP100		-2.0
PromoterAI		0.096	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Other links and lift over

dbSNP: rs564253011; hg19: chr17-61678275;