Variant 11-236091-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_012239.6(SIRT3):c.238C>T(p.Arg80Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 1,561,618 control chromosomes in the GnomAD database, including 19,156 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 (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.13 ( 1471 hom., cov: 32)

Exomes 𝑓: 0.15 ( 17685 hom. )

Consequence

SIRT3
NM_012239.6 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.0360

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008159429).

BP6

Variant 11-236091-G-A is Benign according to our data. Variant chr11-236091-G-A is described in ClinVar as [Benign]. Clinvar id is 3057000.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIRT3	NM_012239.6 linkuse as main transcript	c.238C>T	p.Arg80Trp	missense_variant	1/7	ENST00000382743.9	NP_036371.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIRT3	ENST00000382743.9 linkuse as main transcript	c.238C>T	p.Arg80Trp	missense_variant	1/7	1	NM_012239.6	ENSP00000372191	A2	Q9NTG7-1

Frequencies

GnomAD3 genomes

AF:

0.129

AC:

19568

AN:

152102

Hom.:

1471

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0853

Gnomad AMI

AF:

0.143

Gnomad AMR

AF:

0.135

Gnomad ASJ

AF:

0.159

Gnomad EAS

AF:

0.133

Gnomad SAS

AF:

0.337

Gnomad FIN

AF:

0.0976

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.142

Gnomad OTH

AF:

0.123

GnomAD3 exomes

AF:

0.160

AC:

30303

AN:

188822

Hom.:

2965

AF XY:

0.171

AC XY:

17770

AN XY:

103912

show subpopulations

Gnomad AFR exome

AF:

0.0840

Gnomad AMR exome

AF:

0.122

Gnomad ASJ exome

AF:

0.173

Gnomad EAS exome

AF:

0.125

Gnomad SAS exome

AF:

0.350

Gnomad FIN exome

AF:

0.101

Gnomad NFE exome

AF:

0.143

Gnomad OTH exome

AF:

0.154

GnomAD4 exome

AF:

0.150

AC:

210798

AN:

1409396

Hom.:

17685

Cov.:

AF XY:

0.155

AC XY:

108375

AN XY:

697412

show subpopulations

Gnomad4 AFR exome

AF:

0.0862

Gnomad4 AMR exome

AF:

0.120

Gnomad4 ASJ exome

AF:

0.160

Gnomad4 EAS exome

AF:

0.143

Gnomad4 SAS exome

AF:

0.341

Gnomad4 FIN exome

AF:

0.104

Gnomad4 NFE exome

AF:

0.140

Gnomad4 OTH exome

AF:

0.148

GnomAD4 genome

AF:

0.129

AC:

19565

AN:

152222

Hom.:

1471

Cov.:

AF XY:

0.131

AC XY:

9774

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.0851

Gnomad4 AMR

AF:

0.134

Gnomad4 ASJ

AF:

0.159

Gnomad4 EAS

AF:

0.133

Gnomad4 SAS

AF:

0.338

Gnomad4 FIN

AF:

0.0976

Gnomad4 NFE

AF:

0.142

Gnomad4 OTH

AF:

0.121

Alfa

AF:

0.140

Hom.:

2289

Bravo

AF:

0.121

TwinsUK

AF:

0.138

AC:

511

ALSPAC

AF:

0.148

AC:

569

ESP6500AA

AF:

0.0837

AC:

367

ESP6500EA

AF:

0.142

AC:

1217

ExAC

AF:

0.144

AC:

17301

Asia WGS

AF:

0.207

AC:

720

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SIRT3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 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

0.15

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.75

DEOGEN2

Benign

0.26

T;T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0063

LIST_S2

Benign

0.75

T;T;T

MetaRNN

Benign

0.0082

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;.;.

MutationTaster

Benign

1.0

P;P;P;P;P

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.85

N;N;N

REVEL

Benign

0.14

Sift

Uncertain

0.0010

D;D;T

Sift4G

Uncertain

0.018

D;D;D

Polyphen

0.0040

B;B;B

Vest4

0.059

MPC

0.55

ClinPred

0.075

GERP RS

-0.17

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.28

gMVP

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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