dbSNP rs3829998: SIRT3:c.707-199T>C (chr11-230751-A-G) – 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.707-199T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.771 in 388,890 control chromosomes in the GnomAD database, including 116,350 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 0.79 ( 48163 hom., cov: 32)

Exomes 𝑓: 0.76 ( 68187 hom. )

Consequence

SIRT3
NM_012239.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.508

Publications

11 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 (AFR) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIRT3	NM_012239.6 link	c.707-199T>C		intron_variant	Intron 3 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.707-199T>C		intron_variant	Intron 3 of 6	1	NM_012239.6	ENSP00000372191.4		Q9NTG7-1

Frequencies

GnomAD3 genomes

AF:

0.793

AC:

120506

AN:

152034

Hom.:

48111

Cov.:

show subpopulations

Gnomad AFR

AF:

0.891

Gnomad AMI

AF:

0.731

Gnomad AMR

AF:

0.806

Gnomad ASJ

AF:

0.670

Gnomad EAS

AF:

0.827

Gnomad SAS

AF:

0.797

Gnomad FIN

AF:

0.765

Gnomad MID

AF:

0.655

Gnomad NFE

AF:

0.740

Gnomad OTH

AF:

0.761

GnomAD4 exome

AF:

0.757

AC:

179218

AN:

236738

Hom.:

68187

Cov.:

AF XY:

0.754

AC XY:

90770

AN XY:

120396

show subpopulations

African (AFR)

AF:

0.883

AC:

6075

AN:

6878

American (AMR)

AF:

0.821

AC:

5759

AN:

7012

Ashkenazi Jewish (ASJ)

AF:

0.678

AC:

6040

AN:

8906

East Asian (EAS)

AF:

0.842

AC:

18315

AN:

21762

South Asian (SAS)

AF:

0.788

AC:

2663

AN:

3380

European-Finnish (FIN)

AF:

0.761

AC:

15219

AN:

20002

Middle Eastern (MID)

AF:

0.717

AC:

889

AN:

1240

European-Non Finnish (NFE)

AF:

0.740

AC:

112446

AN:

151994

Other (OTH)

AF:

0.759

AC:

11812

AN:

15564

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1975

3950

5925

7900

9875

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

404

808

1212

1616

2020

<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:

0.793

AC:

120611

AN:

152152

Hom.:

48163

Cov.:

AF XY:

0.796

AC XY:

59175

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.891

AC:

36982

AN:

41518

American (AMR)

AF:

0.807

AC:

12326

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.670

AC:

2325

AN:

3472

East Asian (EAS)

AF:

0.827

AC:

4276

AN:

5168

South Asian (SAS)

AF:

0.797

AC:

3845

AN:

4824

European-Finnish (FIN)

AF:

0.765

AC:

8088

AN:

10576

Middle Eastern (MID)

AF:

0.650

AC:

191

AN:

294

European-Non Finnish (NFE)

AF:

0.740

AC:

50313

AN:

67996

Other (OTH)

AF:

0.757

AC:

1598

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

1313

2626

3939

5252

6565

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

870

1740

2610

3480

4350

<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:

0.714

Hom.:

2337

Bravo

AF:

0.801

Asia WGS

AF:

0.806

AC:

2805

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.87

(source)

DANN

Benign

0.31

PhyloP100

-0.51

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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