rs35252424

Positions:

chr17-63606358-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_016360.4(TACO1):c.433G>A(p.Gly145Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00266 in 1,614,034 control chromosomes in the GnomAD database, including 89 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 47 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 42 hom. )

Consequence

TACO1
NM_016360.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 8.08

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0072649717).

BP6

Variant 17-63606358-G-A is Benign according to our data. Variant chr17-63606358-G-A is described in ClinVar as [Benign]. Clinvar id is 139386.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0134 (2037/152288) while in subpopulation AFR AF= 0.0455 (1892/41550). AF 95% confidence interval is 0.0438. There are 47 homozygotes in gnomad4. There are 908 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 47 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TACO1	NM_016360.4 linkuse as main transcript	c.433G>A	p.Gly145Ser	missense_variant	3/5	ENST00000258975.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
TACO1	ENST00000258975.7 linkuse as main transcript	c.433G>A	p.Gly145Ser	missense_variant	3/5	1	NM_016360.4	P3
TACO1	ENST00000684587.1 linkuse as main transcript	c.430G>A	p.Gly144Ser	missense_variant	3/5			A1
TACO1	ENST00000581120.1 linkuse as main transcript	n.635G>A		non_coding_transcript_exon_variant	3/4	2
TACO1	ENST00000682060.1 linkuse as main transcript	n.195G>A		non_coding_transcript_exon_variant	3/5

Frequencies

GnomAD3 genomes

AF:

0.0134

AC:

2033

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0456

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00687

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.00812

GnomAD3 exomes

AF:

0.00385

AC:

967

AN:

251492

Hom.:

AF XY:

0.00308

AC XY:

419

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.0488

Gnomad AMR exome

AF:

0.00306

Gnomad ASJ exome

AF:

0.00119

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000264

Gnomad OTH exome

AF:

0.00358

GnomAD4 exome

AF:

0.00154

AC:

2254

AN:

1461746

Hom.:

Cov.:

AF XY:

0.00139

AC XY:

1014

AN XY:

727172

show subpopulations

Gnomad4 AFR exome

AF:

0.0477

Gnomad4 AMR exome

AF:

0.00322

Gnomad4 ASJ exome

AF:

0.000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000214

Gnomad4 OTH exome

AF:

0.00389

GnomAD4 genome

AF:

0.0134

AC:

2037

AN:

152288

Hom.:

Cov.:

AF XY:

0.0122

AC XY:

908

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0455

Gnomad4 AMR

AF:

0.00686

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.00803

Alfa

AF:

0.00342

Hom.:

Bravo

AF:

0.0157

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0438

AC:

193

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00441

AC:

536

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 15, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Dec 30, 2016	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Mar 16, 2016	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 04, 2012

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Mitochondrial complex IV deficiency, nuclear type 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Sep 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

TACO1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 13, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.19

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.49

Eigen

Pathogenic

0.92

Eigen_PC

Pathogenic

0.87

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.85

MetaRNN

Benign

0.0073

MetaSVM

Benign

-0.48

MutationAssessor

Pathogenic

3.2

MutationTaster

Benign

1.0

PrimateAI

Benign

0.48

PROVEAN

Pathogenic

-5.5

REVEL

Uncertain

0.39

Sift

Uncertain

0.011

Sift4G

Uncertain

0.011

Polyphen

1.0

Vest4

0.82

MVP

0.36

MPC

1.2

ClinPred

0.038

GERP RS

5.8

Varity_R

0.73

gMVP

0.80

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over