11-223272-A-G

Position:

• chr11-223272-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.287

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIRT3	NM_012239.6	c.969+806T>C		intron_variant		ENST00000382743.9	NP_036371.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIRT3	ENST00000382743.9	c.969+806T>C		intron_variant		1	NM_012239.6	ENSP00000372191.4

Frequencies

GnomAD3 genomes AF: 0.751 AC: 114094 AN: 151858 Hom.: 43305 Cov.: 31

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.: 0 AF XY: 0.679 AC XY: 8503 AN XY: 12522

Gnomad4 AFR exome AF: 0.850

Gnomad4 AMR exome AF: 0.742

Gnomad4 ASJ exome AF: 0.673

Gnomad4 EAS exome AF: 0.606

Gnomad4 SAS exome AF: 0.673

Gnomad4 FIN exome AF: 0.684

Gnomad4 NFE exome AF: 0.667

Gnomad4 OTH exome AF: 0.665

GnomAD4 genome AF: 0.751 AC: 114189 AN: 151976 Hom.: 43345 Cov.: 31 AF XY: 0.753 AC XY: 55962 AN XY: 74294

Gnomad4 AFR AF: 0.859

Gnomad4 AMR AF: 0.752

Gnomad4 ASJ AF: 0.670

Gnomad4 EAS AF: 0.694

Gnomad4 SAS AF: 0.698

Gnomad4 FIN AF: 0.745

Gnomad4 NFE AF: 0.701

Gnomad4 OTH AF: 0.710

Alfa AF: 0.706 Hom.: 50120

Bravo AF: 0.758

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	-0.94
CADD	Benign	1.1
DANN	Benign	0.16
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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

Other links and lift over

dbSNP: rs3782115; hg19: chr11-223272; COSMIC: COSV66953447; COSMIC: COSV66953447;