dbSNP rs3782117: SIRT3:c.969+1142A>G (chr11-222936-T-C) – 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+1142A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 152,274 control chromosomes in the GnomAD database, including 2,438 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 0.16 ( 2435 hom., cov: 33)

Exomes 𝑓: 0.16 ( 3 hom. )

Consequence

SIRT3
NM_012239.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.244

Publications

2 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=-0.96).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.21 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.969+1142A>G	intron	N/A	NP_036371.1	Q9NTG7-1
SIRT3	NM_001370310.1		c.969+1142A>G	intron	N/A	NP_001357239.1
SIRT3	NM_001370312.1		c.777+1142A>G	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.969+1142A>G	intron	N/A	ENSP00000372191.4	Q9NTG7-1
SIRT3	ENST00000941617.1		c.1014+1142A>G	intron	N/A	ENSP00000611676.1
SIRT3	ENST00000852931.1		c.969+1142A>G	intron	N/A	ENSP00000522990.1

Frequencies

GnomAD3 genomes

AF:

0.160

AC:

24355

AN:

152056

Hom.:

2437

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0395

Gnomad AMI

AF:

0.380

Gnomad AMR

AF:

0.188

Gnomad ASJ

AF:

0.252

Gnomad EAS

AF:

0.111

Gnomad SAS

AF:

0.154

Gnomad FIN

AF:

0.223

Gnomad MID

AF:

0.234

Gnomad NFE

AF:

0.213

Gnomad OTH

AF:

0.181

GnomAD4 exome

AF:

0.160

AC:

AN:

100

Hom.:

Cov.:

AF XY:

0.190

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.107

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.160

AC:

AN:

Other (OTH)

AF:

0.188

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.160

AC:

24345

AN:

152174

Hom.:

2435

Cov.:

AF XY:

0.161

AC XY:

11946

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.0395

AC:

1641

AN:

41550

American (AMR)

AF:

0.188

AC:

2871

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.252

AC:

875

AN:

3470

East Asian (EAS)

AF:

0.112

AC:

577

AN:

5168

South Asian (SAS)

AF:

0.154

AC:

743

AN:

4828

European-Finnish (FIN)

AF:

0.223

AC:

2356

AN:

10578

Middle Eastern (MID)

AF:

0.221

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.213

AC:

14494

AN:

67982

Other (OTH)

AF:

0.178

AC:

376

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1038

2076

3115

4153

5191

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

270

540

810

1080

1350

<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:

0.174

Hom.:

353

Bravo

AF:

0.152

Asia WGS

AF:

0.128

AC:

447

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

3.1

(source)

DANN

Benign

0.41

PhyloP100

0.24

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