rs3782117

Positions:

• chr11-222936-T-C

Variant summary

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

The NM_012239.6(SIRT3):​c.969+1142A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 152,274 control chromosomes in the GnomAD database, including 2,438 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 0.16 (2435 hom., cov: 33)
  • Exomes 𝑓: 0.16 (3 hom.)
• Consequence: SIRT3 NM_012239.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.244

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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIRT3	NM_012239.6	c.969+1142A>G		intron_variant		ENST00000382743.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIRT3	ENST00000382743.9	c.969+1142A>G		intron_variant		1	NM_012239.6	A2

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24355 AN: 152056 Hom.: 2437 Cov.: 33

Gnomad AFR AF: 0.0395

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.181

GnomAD4 exome AF: 0.160 AC: 16 AN: 100 Hom.: 3 Cov.: 0 AF XY: 0.190 AC XY: 11 AN XY: 58

Gnomad4 AFR exome AF: 0.00

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.107

Gnomad4 NFE exome AF: 0.160

Gnomad4 OTH exome AF: 0.188

GnomAD4 genome AF: 0.160 AC: 24345 AN: 152174 Hom.: 2435 Cov.: 33 AF XY: 0.161 AC XY: 11946 AN XY: 74388

Gnomad4 AFR AF: 0.0395

Gnomad4 AMR AF: 0.188

Gnomad4 ASJ AF: 0.252

Gnomad4 EAS AF: 0.112

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.223

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.178

Alfa AF: 0.180 Hom.: 352

Bravo AF: 0.152

Asia WGS AF: 0.128 AC: 447 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.1
DANN	Benign	0.41

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: rs3782117; hg19: chr11-222936;