rs535716

Positions:

• chr11-218640-G-A
• chr11-218640-G-C

Variant summary

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

The NM_012239.6(SIRT3):​c.1179+192C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 1,059,424 control chromosomes in the GnomAD database, including 29,828 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 0.28 (7303 hom., cov: 32)
  • Exomes 𝑓: 0.21 (22525 hom.)
• Consequence: SIRT3 NM_012239.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0920

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.475 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIRT3	NM_012239.6	c.1179+192C>T		intron_variant		ENST00000382743.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIRT3	ENST00000382743.9	c.1179+192C>T		intron_variant		1	NM_012239.6	A2

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42523 AN: 151896 Hom.: 7287 Cov.: 32

Gnomad AFR AF: 0.480

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.00481

Gnomad SAS AF: 0.0806

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.244

GnomAD4 exome AF: 0.211 AC: 191020 AN: 907410 Hom.: 22525 AF XY: 0.205 AC XY: 92640 AN XY: 452626

Gnomad4 AFR exome AF: 0.476

Gnomad4 AMR exome AF: 0.242

Gnomad4 ASJ exome AF: 0.117

Gnomad4 EAS exome AF: 0.00169

Gnomad4 SAS exome AF: 0.0802

Gnomad4 FIN exome AF: 0.284

Gnomad4 NFE exome AF: 0.222

Gnomad4 OTH exome AF: 0.203

GnomAD4 genome AF: 0.280 AC: 42591 AN: 152014 Hom.: 7303 Cov.: 32 AF XY: 0.278 AC XY: 20658 AN XY: 74308

Gnomad4 AFR AF: 0.480

Gnomad4 AMR AF: 0.216

Gnomad4 ASJ AF: 0.116

Gnomad4 EAS AF: 0.00463

Gnomad4 SAS AF: 0.0805

Gnomad4 FIN AF: 0.289

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.242

Alfa AF: 0.269 Hom.: 811

Bravo AF: 0.287

Asia WGS AF: 0.0790 AC: 278 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.1
DANN	Benign	0.78

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: rs535716; hg19: chr11-218640;