11-223119-T-C

Variant names:

• chr11-223119-T-C
• rs3782116
• NM_012239.6:c.969+959A>G

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+959A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.735 in 153,170 control chromosomes in the GnomAD database, including 41,778 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 0.74 (41524 hom., cov: 31)
  • Exomes 𝑓: 0.63 (254 hom.)
• Consequence: SIRT3 NM_012239.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIRT3	NM_012239.6	c.969+959A>G		intron_variant	Intron 5 of 6	ENST00000382743.9	NP_036371.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIRT3	ENST00000382743.9	c.969+959A>G		intron_variant	Intron 5 of 6	1	NM_012239.6	ENSP00000372191.4

Frequencies

GnomAD3 genomes AF: 0.736 AC: 111707 AN: 151878 Hom.: 41482 Cov.: 31

Gnomad AFR AF: 0.838

Gnomad AMI AF: 0.721

Gnomad AMR AF: 0.730

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.686

Gnomad SAS AF: 0.690

Gnomad FIN AF: 0.737

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.687

Gnomad OTH AF: 0.697

GnomAD4 exome AF: 0.633 AC: 743 AN: 1174 Hom.: 254 Cov.: 0 AF XY: 0.646 AC XY: 408 AN XY: 632

African (AFR) AF: 0.833 AC: 10 AN: 12

American (AMR) AF: 0.643 AC: 72 AN: 112

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 7 AN: 14

East Asian (EAS) AF: 0.250 AC: 1 AN: 4

South Asian (SAS) AF: 0.588 AC: 40 AN: 68

European-Finnish (FIN) AF: 0.955 AC: 21 AN: 22

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.628 AC: 561 AN: 894

Other (OTH) AF: 0.674 AC: 31 AN: 46

GnomAD4 genome AF: 0.736 AC: 111802 AN: 151996 Hom.: 41524 Cov.: 31 AF XY: 0.738 AC XY: 54824 AN XY: 74300

African (AFR) AF: 0.838 AC: 34725 AN: 41440

American (AMR) AF: 0.730 AC: 11142 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.661 AC: 2296 AN: 3472

East Asian (EAS) AF: 0.687 AC: 3536 AN: 5150

South Asian (SAS) AF: 0.690 AC: 3323 AN: 4818

European-Finnish (FIN) AF: 0.737 AC: 7803 AN: 10582

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.687 AC: 46688 AN: 67950

Other (OTH) AF: 0.692 AC: 1457 AN: 2106

Alfa AF: 0.700 Hom.: 46752

Bravo AF: 0.739

Asia WGS AF: 0.684 AC: 2382 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.2
DANN	Benign	0.80
PhyloP100		-1.4
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: rs3782116; hg19: chr11-223119;