rs536715

Variant names:

• chr11-230368-C-T
• rs536715
• NM_012239.6:c.807+84G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 22 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SIRT3	NM_012239.6	c.807+84G>A		intron_variant	Intron 4 of 6	ENST00000382743.9	NP_036371.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIRT3	ENST00000382743.9	c.807+84G>A		intron_variant	Intron 4 of 6	1	NM_012239.6	ENSP00000372191.4

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

African (AFR) AF: 0.169 AC: 2226 AN: 13158

American (AMR) AF: 0.272 AC: 3954 AN: 14548

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 1409 AN: 11634

East Asian (EAS) AF: 0.410 AC: 11334 AN: 27646

South Asian (SAS) AF: 0.124 AC: 2403 AN: 19450

European-Finnish (FIN) AF: 0.108 AC: 4498 AN: 41732

Middle Eastern (MID) AF: 0.106 AC: 372 AN: 3504

European-Non Finnish (NFE) AF: 0.114 AC: 45551 AN: 398224

Other (OTH) AF: 0.147 AC: 3908 AN: 26516

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

African (AFR) AF: 0.172 AC: 7113 AN: 41450

American (AMR) AF: 0.225 AC: 3440 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 415 AN: 3472

East Asian (EAS) AF: 0.432 AC: 2230 AN: 5166

South Asian (SAS) AF: 0.127 AC: 609 AN: 4812

European-Finnish (FIN) AF: 0.101 AC: 1063 AN: 10566

Middle Eastern (MID) AF: 0.103 AC: 30 AN: 292

European-Non Finnish (NFE) AF: 0.112 AC: 7616 AN: 67984

Other (OTH) AF: 0.147 AC: 310 AN: 2114

Alfa AF: 0.132 Hom.: 5617

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
PhyloP100		-0.95
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs536715; hg19: chr11-230368;