dbSNP rs536715: SIRT3:c.807+84G>A (chr11-230368-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_012239.6(SIRT3):c.807+84G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 708,450 control chromosomes in the GnomAD database, including 8,677 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.15 ( 2116 hom., cov: 32)

Exomes 𝑓: 0.14 ( 6561 hom. )

Consequence

SIRT3
NM_012239.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.955

Publications

22 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012239.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SIRT3	NM_012239.6	MANE Select	c.807+84G>A	intron	N/A	NP_036371.1	Q9NTG7-1
SIRT3	NM_001370310.1		c.807+84G>A	intron	N/A	NP_001357239.1
SIRT3	NM_001370312.1		c.615+84G>A	intron	N/A	NP_001357241.1	E9PN58

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SIRT3	ENST00000382743.9	TSL:1 MANE Select	c.807+84G>A	intron	N/A	ENSP00000372191.4	Q9NTG7-1
SIRT3	ENST00000941617.1		c.807+84G>A	intron	N/A	ENSP00000611676.1
SIRT3	ENST00000852931.1		c.807+84G>A	intron	N/A	ENSP00000522990.1

Frequencies

GnomAD3 genomes

AF:

0.150

AC:

22808

AN:

151920

Hom.:

2106

Cov.:

show subpopulations

Gnomad AFR

AF:

0.171

Gnomad AMI

AF:

0.0165

Gnomad AMR

AF:

0.225

Gnomad ASJ

AF:

0.120

Gnomad EAS

AF:

0.431

Gnomad SAS

AF:

0.127

Gnomad FIN

AF:

0.101

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.112

Gnomad OTH

AF:

0.146

GnomAD4 exome

AF:

0.136

AC:

75655

AN:

556412

Hom.:

6561

AF XY:

0.134

AC XY:

37622

AN XY:

281602

show subpopulations

African (AFR)

AF:

0.169

AC:

2226

AN:

13158

American (AMR)

AF:

0.272

AC:

3954

AN:

14548

Ashkenazi Jewish (ASJ)

AF:

0.121

AC:

1409

AN:

11634

East Asian (EAS)

AF:

0.410

AC:

11334

AN:

27646

South Asian (SAS)

AF:

0.124

AC:

2403

AN:

19450

European-Finnish (FIN)

AF:

0.108

AC:

4498

AN:

41732

Middle Eastern (MID)

AF:

0.106

AC:

372

AN:

3504

European-Non Finnish (NFE)

AF:

0.114

AC:

45551

AN:

398224

Other (OTH)

AF:

0.147

AC:

3908

AN:

26516

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

3110

6220

9331

12441

15551

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1464

2928

4392

5856

7320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.150

AC:

22841

AN:

152038

Hom.:

2116

Cov.:

AF XY:

0.152

AC XY:

11302

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.172

AC:

7113

AN:

41450

American (AMR)

AF:

0.225

AC:

3440

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.120

AC:

415

AN:

3472

East Asian (EAS)

AF:

0.432

AC:

2230

AN:

5166

South Asian (SAS)

AF:

0.127

AC:

609

AN:

4812

European-Finnish (FIN)

AF:

0.101

AC:

1063

AN:

10566

Middle Eastern (MID)

AF:

0.103

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.112

AC:

7616

AN:

67984

Other (OTH)

AF:

0.147

AC:

310

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

965

1931

2896

3862

4827

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

248

496

744

992

1240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.132

Hom.:

5617

Bravo

AF:

0.167

Asia WGS

AF:

0.259

AC:

898

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.41

(source)

DANN

Benign

0.26

PhyloP100

-0.95

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over