dbSNP rs12222188: SIRT3:c.969+15C>T (chr11-224063-G-A) – 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.969+15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0464 in 1,602,992 control chromosomes in the GnomAD database, including 2,692 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 0.048 ( 338 hom., cov: 31)

Exomes 𝑓: 0.046 ( 2354 hom. )

Consequence

SIRT3
NM_012239.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.503

Publications

9 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=-0.83).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIRT3	NM_012239.6 link	c.969+15C>T		intron_variant	Intron 5 of 6	ENST00000382743.9	NP_036371.1	Q9NTG7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIRT3	ENST00000382743.9 link	c.969+15C>T		intron_variant	Intron 5 of 6	1	NM_012239.6	ENSP00000372191.4		Q9NTG7-1

Frequencies

GnomAD3 genomes

AF:

0.0477

AC:

7163

AN:

150284

Hom.:

338

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0588

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0643

Gnomad ASJ

AF:

0.0149

Gnomad EAS

AF:

0.141

Gnomad SAS

AF:

0.0948

Gnomad FIN

AF:

0.0189

Gnomad MID

AF:

0.0296

Gnomad NFE

AF:

0.0338

Gnomad OTH

AF:

0.0409

GnomAD2 exomes

AF:

0.0564

AC:

14133

AN:

250800

AF XY:

0.0575

show subpopulations

Gnomad AFR exome

AF:

0.0627

Gnomad AMR exome

AF:

0.0676

Gnomad ASJ exome

AF:

0.0188

Gnomad EAS exome

AF:

0.132

Gnomad FIN exome

AF:

0.0189

Gnomad NFE exome

AF:

0.0380

Gnomad OTH exome

AF:

0.0510

GnomAD4 exome

AF:

0.0462

AC:

67174

AN:

1452590

Hom.:

2354

Cov.:

AF XY:

0.0472

AC XY:

34047

AN XY:

721970

show subpopulations

African (AFR)

AF:

0.0634

AC:

2110

AN:

33302

American (AMR)

AF:

0.0654

AC:

2908

AN:

44452

Ashkenazi Jewish (ASJ)

AF:

0.0160

AC:

415

AN:

25896

East Asian (EAS)

AF:

0.126

AC:

4974

AN:

39538

South Asian (SAS)

AF:

0.0926

AC:

7759

AN:

83768

European-Finnish (FIN)

AF:

0.0187

AC:

990

AN:

53018

Middle Eastern (MID)

AF:

0.0481

AC:

274

AN:

5692

European-Non Finnish (NFE)

AF:

0.0405

AC:

44818

AN:

1107006

Other (OTH)

AF:

0.0488

AC:

2926

AN:

59918

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

3148

6297

9445

12594

15742

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1950

3900

5850

7800

9750

<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:

0.0477

AC:

7172

AN:

150402

Hom.:

338

Cov.:

AF XY:

0.0479

AC XY:

3522

AN XY:

73490

show subpopulations

African (AFR)

AF:

0.0587

AC:

2418

AN:

41192

American (AMR)

AF:

0.0650

AC:

980

AN:

15070

Ashkenazi Jewish (ASJ)

AF:

0.0149

AC:

AN:

3426

East Asian (EAS)

AF:

0.141

AC:

720

AN:

5112

South Asian (SAS)

AF:

0.0945

AC:

442

AN:

4678

European-Finnish (FIN)

AF:

0.0189

AC:

198

AN:

10466

Middle Eastern (MID)

AF:

0.0282

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.0338

AC:

2269

AN:

67190

Other (OTH)

AF:

0.0415

AC:

AN:

2074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.528

Heterozygous variant carriers

289

578

867

1156

1445

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

252

336

420

<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:

0.0360

Hom.:

Bravo

AF:

0.0555

Asia WGS

AF:

0.118

AC:

407

AN:

3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

(source)

DANN

Benign

0.44

PhyloP100

0.50

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over