rs11246007

Variant names:

• chr11-221584-C-T
• rs11246007
• NM_012239.6:c.969+2494G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012239.6(SIRT3):​c.969+2494G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 152,190 control chromosomes in the GnomAD database, including 1,788 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 0.15 (1788 hom., cov: 33)
• Consequence: SIRT3 NM_012239.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• Publications: 18 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.327 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIRT3	NM_012239.6	MANE Select	c.969+2494G>A		intron	N/A	NP_036371.1	Q9NTG7-1
	SIRT3	NM_001370310.1		c.969+2494G>A		intron	N/A	NP_001357239.1
	SIRT3	NM_001370312.1		c.777+2494G>A		intron	N/A	NP_001357241.1	E9PN58

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIRT3	ENST00000382743.9	TSL:1 MANE Select	c.969+2494G>A		intron	N/A	ENSP00000372191.4	Q9NTG7-1
	SIRT3	ENST00000941617.1		c.1014+2494G>A		intron	N/A	ENSP00000611676.1
	SIRT3	ENST00000852931.1		c.969+2494G>A		intron	N/A	ENSP00000522990.1

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22431 AN: 152072 Hom.: 1787 Cov.: 33

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.137

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.147 AC: 22431 AN: 152190 Hom.: 1788 Cov.: 33 AF XY: 0.149 AC XY: 11105 AN XY: 74392

African (AFR) AF: 0.122 AC: 5063 AN: 41518

American (AMR) AF: 0.141 AC: 2158 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 554 AN: 3470

East Asian (EAS) AF: 0.132 AC: 682 AN: 5186

South Asian (SAS) AF: 0.340 AC: 1639 AN: 4814

European-Finnish (FIN) AF: 0.113 AC: 1192 AN: 10580

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10670 AN: 68016

Other (OTH) AF: 0.135 AC: 286 AN: 2112

Alfa AF: 0.153 Hom.: 5859

Bravo AF: 0.141

Asia WGS AF: 0.212 AC: 737 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.45
DANN	Benign	0.44
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11246007; hg19: chr11-221584;