Variant rs11555236 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BA1

The NM_012239.6(SIRT3):c.477G>T(p.Ser159Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 1,611,950 control chromosomes in the GnomAD database, including 32,023 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.16 ( 2339 hom., cov: 31)

Exomes 𝑓: 0.20 ( 29684 hom. )

Consequence

SIRT3
NM_012239.6 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.384

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:

SIRT3 (HGNC:):

SIRT3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant 11-233212-C-A is Benign according to our data. Variant chr11-233212-C-A is described in ClinVar as [Benign]. Clinvar id is 3060621.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.384 with no splicing effect.

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	Protein	UniProt
SIRT3	NM_012239.6 linkuse as main transcript	c.477G>T	p.Ser159Ser	synonymous_variant	3/7	ENST00000382743.9	NP_036371.1	Q9NTG7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIRT3	ENST00000382743.9 linkuse as main transcript	c.477G>T	p.Ser159Ser	synonymous_variant	3/7	1	NM_012239.6	ENSP00000372191.4		Q9NTG7-1

Frequencies

GnomAD3 genomes

AF:

0.156

AC:

23745

AN:

151826

Hom.:

2341

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0389

Gnomad AMI

AF:

0.380

Gnomad AMR

AF:

0.154

Gnomad ASJ

AF:

0.252

Gnomad EAS

AF:

0.112

Gnomad SAS

AF:

0.148

Gnomad FIN

AF:

0.224

Gnomad MID

AF:

0.234

Gnomad NFE

AF:

0.213

Gnomad OTH

AF:

0.182

GnomAD3 exomes

AF:

0.170

AC:

42446

AN:

250078

Hom.:

4101

AF XY:

0.176

AC XY:

23729

AN XY:

135144

show subpopulations

Gnomad AFR exome

AF:

0.0332

Gnomad AMR exome

AF:

0.106

Gnomad ASJ exome

AF:

0.262

Gnomad EAS exome

AF:

0.0957

Gnomad SAS exome

AF:

0.142

Gnomad FIN exome

AF:

0.220

Gnomad NFE exome

AF:

0.209

Gnomad OTH exome

AF:

0.190

GnomAD4 exome

AF:

0.197

AC:

287785

AN:

1460006

Hom.:

29684

Cov.:

AF XY:

0.197

AC XY:

143090

AN XY:

726092

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:

23734

AN:

151944

Hom.:

2339

Cov.:

AF XY:

0.156

AC XY:

11608

AN XY:

74218

show subpopulations

Gnomad4 AFR

AF:

0.0390

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:

0.178

Hom.:

1652

Bravo

AF:

0.146

Asia WGS

AF:

0.123

AC:

430

AN:

3478

EpiCase

AF:

0.232

EpiControl

AF:

0.230

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 23, 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

BayesDel_noAF

Benign

-0.34

CADD

Benign

9.9

DANN

Benign

0.74

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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