rs12222188

Variant summary

Our verdict is Benign. Variant got -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

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.503
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons MANE Protein UniProt
SIRT3NM_012239.6 linkc.969+15C>T intron_variant ENST00000382743.9 NP_036371.1 Q9NTG7-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SIRT3ENST00000382743.9 linkc.969+15C>T intron_variant 1 NM_012239.6 ENSP00000372191.4 Q9NTG7-1

Frequencies

GnomAD3 genomes
AF:
0.0477
AC:
7163
AN:
150284
Hom.:
338
Cov.:
31
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
GnomAD3 exomes
AF:
0.0564
AC:
14133
AN:
250800
Hom.:
595
AF XY:
0.0575
AC XY:
7796
AN XY:
135624
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 SAS exome
AF:
0.103
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.:
33
AF XY:
0.0472
AC XY:
34047
AN XY:
721970
show subpopulations
Gnomad4 AFR exome
AF:
0.0634
Gnomad4 AMR exome
AF:
0.0654
Gnomad4 ASJ exome
AF:
0.0160
Gnomad4 EAS exome
AF:
0.126
Gnomad4 SAS exome
AF:
0.0926
Gnomad4 FIN exome
AF:
0.0187
Gnomad4 NFE exome
AF:
0.0405
Gnomad4 OTH exome
AF:
0.0488
GnomAD4 genome
AF:
0.0477
AC:
7172
AN:
150402
Hom.:
338
Cov.:
31
AF XY:
0.0479
AC XY:
3522
AN XY:
73490
show subpopulations
Gnomad4 AFR
AF:
0.0587
Gnomad4 AMR
AF:
0.0650
Gnomad4 ASJ
AF:
0.0149
Gnomad4 EAS
AF:
0.141
Gnomad4 SAS
AF:
0.0945
Gnomad4 FIN
AF:
0.0189
Gnomad4 NFE
AF:
0.0338
Gnomad4 OTH
AF:
0.0415
Alfa
AF:
0.0318
Hom.:
39
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
12
DANN
Benign
0.44

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs12222188; hg19: chr11-224063; API