Variant 11-233067-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_012239.6(SIRT3):c.622G>A(p.Val208Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 1,613,830 control chromosomes in the GnomAD database, including 32,075 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.16 ( 2346 hom., cov: 31)

Exomes 𝑓: 0.20 ( 29729 hom. )

Consequence

SIRT3
NM_012239.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.829

Variant links:

Genes affected

SIRT3 (HGNC:14931): (sirtuin 3) SIRT3 encodes a member of the sirtuin family of class III histone deacetylases, homologs to the yeast Sir2 protein. The encoded protein is found exclusively in mitochondria, where it can eliminate reactive oxygen species, inhibit apoptosis, and prevent the formation of cancer cells. SIRT3 has far-reaching effects on nuclear gene expression, cancer, cardiovascular disease, neuroprotection, aging, and metabolic control. [provided by RefSeq, May 2019]

SIRT3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0025118291).

BP6

Variant 11-233067-C-T is Benign according to our data. Variant chr11-233067-C-T is described in ClinVar as [Benign]. Clinvar id is 3060261.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIRT3	NM_012239.6 linkuse as main transcript	c.622G>A	p.Val208Ile	missense_variant	3/7	ENST00000382743.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIRT3	ENST00000382743.9 linkuse as main transcript	c.622G>A	p.Val208Ile	missense_variant	3/7	1	NM_012239.6	A2	Q9NTG7-1

Frequencies

GnomAD3 genomes

AF:

0.156

AC:

23750

AN:

151932

Hom.:

2348

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0388

Gnomad AMI

AF:

0.382

Gnomad AMR

AF:

0.154

Gnomad ASJ

AF:

0.252

Gnomad EAS

AF:

0.112

Gnomad SAS

AF:

0.147

Gnomad FIN

AF:

0.224

Gnomad MID

AF:

0.232

Gnomad NFE

AF:

0.213

Gnomad OTH

AF:

0.182

GnomAD3 exomes

AF:

0.170

AC:

42782

AN:

251474

Hom.:

4175

AF XY:

0.176

AC XY:

23936

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.0330

Gnomad AMR exome

AF:

0.106

Gnomad ASJ exome

AF:

0.261

Gnomad EAS exome

AF:

0.0960

Gnomad SAS exome

AF:

0.142

Gnomad FIN exome

AF:

0.220

Gnomad NFE exome

AF:

0.210

Gnomad OTH exome

AF:

0.191

GnomAD4 exome

AF:

0.197

AC:

288203

AN:

1461780

Hom.:

29729

Cov.:

AF XY:

0.197

AC XY:

143334

AN XY:

727186

show subpopulations

Gnomad4 AFR exome

AF:

0.0344

Gnomad4 AMR exome

AF:

0.112

Gnomad4 ASJ exome

AF:

0.259

Gnomad4 EAS exome

AF:

0.134

Gnomad4 SAS exome

AF:

0.141

Gnomad4 FIN exome

AF:

0.214

Gnomad4 NFE exome

AF:

0.210

Gnomad4 OTH exome

AF:

0.191

GnomAD4 genome

AF:

0.156

AC:

23737

AN:

152050

Hom.:

2346

Cov.:

AF XY:

0.156

AC XY:

11602

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.0388

Gnomad4 AMR

AF:

0.153

Gnomad4 ASJ

AF:

0.252

Gnomad4 EAS

AF:

0.112

Gnomad4 SAS

AF:

0.147

Gnomad4 FIN

AF:

0.224

Gnomad4 NFE

AF:

0.213

Gnomad4 OTH

AF:

0.180

Alfa

AF:

0.208

Hom.:

8589

Bravo

AF:

0.146

ESP6500AA

AF:

0.0433

AC:

191

ESP6500EA

AF:

0.213

AC:

1831

ExAC

AF:

0.166

AC:

20202

Asia WGS

AF:

0.124

AC:

431

AN:

3478

EpiCase

AF:

0.232

EpiControl

AF:

0.231

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

SIRT3-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 27, 2019

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

0.068

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.54

CADD

Benign

0.090

DANN

Benign

0.82

DEOGEN2

Benign

0.047

T;.;T;.;.;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.038

LIST_S2

Benign

0.30

T;T;T;T;T;T

MetaRNN

Benign

0.0025

T;T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.85

N;.;.;.;.;.

MutationTaster

Benign

1.0

P;P;P;P;P

PrimateAI

Benign

0.23

PROVEAN

Benign

0.040

N;N;N;N;N;N

REVEL

Benign

0.12

Sift

Benign

1.0

T;T;T;T;T;T

Sift4G

Benign

0.78

T;T;T;T;T;.

Polyphen

0.0020

B;B;B;B;.;.

Vest4

0.055

MPC

0.15

ClinPred

0.0019

GERP RS

-3.3

Varity_R

0.051

gMVP

0.59

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