17-63601182-G-A

Variant names:

• chr17-63601182-G-A
• rs1195907944
• NM_016360.4:c.99G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_016360.4(TACO1):​c.99G>A​(p.Arg33Arg) variant causes a synonymous 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TACO1 NM_016360.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.469
• 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 -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 17-63601182-G-A is Benign according to our data. Variant chr17-63601182-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2017897.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.469 with no splicing effect.

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.99G>A	p.Arg33Arg	synonymous	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.99G>A	p.Arg33Arg	synonymous	Exon 1 of 5	ENSP00000258975.6	Q9BSH4
	ENSG00000288894	ENST00000690765.1		n.*107-3352G>A		intron	N/A	ENSP00000510085.1
	TACO1	ENST00000684587.1		c.99G>A	p.Arg33Arg	synonymous	Exon 1 of 5	ENSP00000507435.1	A0A804HJB7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1399644 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 690522

African (AFR) AF: 0.00 AC: 0 AN: 31926

American (AMR) AF: 0.00 AC: 0 AN: 35940

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25124

East Asian (EAS) AF: 0.00 AC: 0 AN: 36234

South Asian (SAS) AF: 0.00 AC: 0 AN: 79714

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47550

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4400

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1080826

Other (OTH) AF: 0.00 AC: 0 AN: 57930

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.8
DANN	Benign	0.79
PhyloP100		0.47
PromoterAI		-0.041	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: rs1195907944; hg19: chr17-61678541;