Genetic Variant SIRT3:c.969+806T>C (chr11-223272-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.969+806T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.741 in 176,526 control chromosomes in the GnomAD database, including 49,172 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 0.75 ( 43345 hom., cov: 31)

Exomes 𝑓: 0.68 ( 5827 hom. )

Consequence

SIRT3
NM_012239.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.287

Publications

23 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:

Genome browser will be placed here

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=-0.94).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.851 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
SIRT3	NM_012239.6	MANE Select	c.969+806T>C	intron	N/A	NP_036371.1
SIRT3	NM_001370310.1		c.969+806T>C	intron	N/A	NP_001357239.1
SIRT3	NM_001370312.1		c.777+806T>C	intron	N/A	NP_001357241.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SIRT3	ENST00000382743.9	TSL:1 MANE Select	c.969+806T>C	intron	N/A	ENSP00000372191.4
SIRT3	ENST00000529937.1	TSL:5	n.*482T>C	non_coding_transcript_exon	Exon 3 of 5	ENSP00000434747.1
SIRT3	ENST00000529937.1	TSL:5	n.*482T>C	3_prime_UTR	Exon 3 of 5	ENSP00000434747.1

Frequencies

GnomAD3 genomes

AF:

0.751

AC:

114094

AN:

151858

Hom.:

43305

Cov.:

show subpopulations

Gnomad AFR

AF:

0.859

Gnomad AMI

AF:

0.723

Gnomad AMR

AF:

0.752

Gnomad ASJ

AF:

0.670

Gnomad EAS

AF:

0.693

Gnomad SAS

AF:

0.698

Gnomad FIN

AF:

0.745

Gnomad MID

AF:

0.614

Gnomad NFE

AF:

0.701

Gnomad OTH

AF:

0.715

GnomAD4 exome

AF:

0.680

AC:

16701

AN:

24550

Hom.:

5827

Cov.:

AF XY:

0.679

AC XY:

8503

AN XY:

12522

show subpopulations

African (AFR)

AF:

0.850

AC:

680

AN:

800

American (AMR)

AF:

0.742

AC:

1848

AN:

2492

Ashkenazi Jewish (ASJ)

AF:

0.673

AC:

296

AN:

440

East Asian (EAS)

AF:

0.606

AC:

405

AN:

668

South Asian (SAS)

AF:

0.673

AC:

2073

AN:

3082

European-Finnish (FIN)

AF:

0.684

AC:

580

AN:

848

Middle Eastern (MID)

AF:

0.650

AC:

AN:

100

European-Non Finnish (NFE)

AF:

0.667

AC:

9864

AN:

14782

Other (OTH)

AF:

0.665

AC:

890

AN:

1338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

241

481

722

962

1203

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

130

260

390

520

650

<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:

0.751

AC:

114189

AN:

151976

Hom.:

43345

Cov.:

AF XY:

0.753

AC XY:

55962

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.859

AC:

35588

AN:

41448

American (AMR)

AF:

0.752

AC:

11484

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.670

AC:

2323

AN:

3468

East Asian (EAS)

AF:

0.694

AC:

3566

AN:

5142

South Asian (SAS)

AF:

0.698

AC:

3357

AN:

4808

European-Finnish (FIN)

AF:

0.745

AC:

7880

AN:

10574

Middle Eastern (MID)

AF:

0.616

AC:

181

AN:

294

European-Non Finnish (NFE)

AF:

0.701

AC:

47659

AN:

67950

Other (OTH)

AF:

0.710

AC:

1493

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1439

2878

4317

5756

7195

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

846

1692

2538

3384

4230

<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:

0.713

Hom.:

71424

Bravo

AF:

0.758

Asia WGS

AF:

0.684

AC:

2382

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

1.1

(source)

DANN

Benign

0.16

PhyloP100

-0.29

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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