11-219089-T-C

Position:

• chr11-219089-T-C

Variant summary

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

The ENST00000382743.9(SIRT3):​c.970-48A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.705 in 1,550,270 control chromosomes in the GnomAD database, including 387,064 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 0.71 (38501 hom., cov: 31)
  • Exomes 𝑓: 0.70 (348563 hom.)
• Consequence: SIRT3 ENST00000382743.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0220

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIRT3	NM_012239.6	c.970-48A>G		intron_variant		ENST00000382743.9	NP_036371.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIRT3	ENST00000382743.9	c.970-48A>G		intron_variant		1	NM_012239.6	ENSP00000372191.4

Frequencies

GnomAD3 genomes AF: 0.708 AC: 107577 AN: 151880 Hom.: 38471 Cov.: 31

Gnomad AFR AF: 0.756

Gnomad AMI AF: 0.719

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.648

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.722

Gnomad FIN AF: 0.740

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.706

Gnomad OTH AF: 0.679

GnomAD3 exomes AF: 0.681 AC: 116742 AN: 171356 Hom.: 40077 AF XY: 0.684 AC XY: 62322 AN XY: 91102

Gnomad AFR exome AF: 0.753

Gnomad AMR exome AF: 0.626

Gnomad ASJ exome AF: 0.666

Gnomad EAS exome AF: 0.451

Gnomad SAS exome AF: 0.724

Gnomad FIN exome AF: 0.740

Gnomad NFE exome AF: 0.707

Gnomad OTH exome AF: 0.682

GnomAD4 exome AF: 0.705 AC: 985304 AN: 1398272 Hom.: 348563 Cov.: 39 AF XY: 0.705 AC XY: 485408 AN XY: 688788

Gnomad4 AFR exome AF: 0.761

Gnomad4 AMR exome AF: 0.632

Gnomad4 ASJ exome AF: 0.651

Gnomad4 EAS exome AF: 0.483

Gnomad4 SAS exome AF: 0.718

Gnomad4 FIN exome AF: 0.736

Gnomad4 NFE exome AF: 0.713

Gnomad4 OTH exome AF: 0.691

GnomAD4 genome AF: 0.708 AC: 107656 AN: 151998 Hom.: 38501 Cov.: 31 AF XY: 0.709 AC XY: 52654 AN XY: 74306

Gnomad4 AFR AF: 0.756

Gnomad4 AMR AF: 0.659

Gnomad4 ASJ AF: 0.648

Gnomad4 EAS AF: 0.477

Gnomad4 SAS AF: 0.722

Gnomad4 FIN AF: 0.740

Gnomad4 NFE AF: 0.706

Gnomad4 OTH AF: 0.675

Alfa AF: 0.700 Hom.: 51022

Bravo AF: 0.703

Asia WGS AF: 0.633 AC: 2203 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	6.0
DANN	Benign	0.49

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: rs511744; hg19: chr11-219089; COSMIC: COSV57342795; COSMIC: COSV57342795;