rs536715

Positions:

• chr11-230368-C-T

Variant summary

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

The NM_012239.6(SIRT3):​c.807+84G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 708,450 control chromosomes in the GnomAD database, including 8,677 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 (2116 hom., cov: 32)
  • Exomes 𝑓: 0.14 (6561 hom.)
• Consequence: SIRT3 NM_012239.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.955

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIRT3	NM_012239.6	c.807+84G>A		intron_variant		ENST00000382743.9	NP_036371.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIRT3	ENST00000382743.9	c.807+84G>A		intron_variant		1	NM_012239.6	ENSP00000372191	A2

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22808 AN: 151920 Hom.: 2106 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.0165

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.146

GnomAD4 exome AF: 0.136 AC: 75655 AN: 556412 Hom.: 6561 AF XY: 0.134 AC XY: 37622 AN XY: 281602

Gnomad4 AFR exome AF: 0.169

Gnomad4 AMR exome AF: 0.272

Gnomad4 ASJ exome AF: 0.121

Gnomad4 EAS exome AF: 0.410

Gnomad4 SAS exome AF: 0.124

Gnomad4 FIN exome AF: 0.108

Gnomad4 NFE exome AF: 0.114

Gnomad4 OTH exome AF: 0.147

GnomAD4 genome AF: 0.150 AC: 22841 AN: 152038 Hom.: 2116 Cov.: 32 AF XY: 0.152 AC XY: 11302 AN XY: 74306

Gnomad4 AFR AF: 0.172

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.120

Gnomad4 EAS AF: 0.432

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.147

Alfa AF: 0.127 Hom.: 2409

Bravo AF: 0.167

Asia WGS AF: 0.259 AC: 898 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.41
DANN	Benign	0.26

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: rs536715; hg19: chr11-230368;