NM_012239.6:c.706+1003G>C

Variant names:

• chr11-231980-C-G
• rs12363280
• NM_012239.6:c.706+1003G>C

Variant summary

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

The NM_012239.6(SIRT3):​c.706+1003G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 137,902 control chromosomes in the GnomAD database, including 2,356 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 0.17 (2356 hom., cov: 30)
• Consequence: SIRT3 NM_012239.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0900

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 (NFE) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIRT3	NM_012239.6	c.706+1003G>C		intron_variant	Intron 3 of 6	ENST00000382743.9	NP_036371.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIRT3	ENST00000382743.9	c.706+1003G>C		intron_variant	Intron 3 of 6	1	NM_012239.6	ENSP00000372191.4

Frequencies

GnomAD3 genomes AF: 0.172 AC: 23756 AN: 137788 Hom.: 2358 Cov.: 30

Gnomad AFR AF: 0.0428

Gnomad AMI AF: 0.410

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.274

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.198

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.172 AC: 23742 AN: 137902 Hom.: 2356 Cov.: 30 AF XY: 0.173 AC XY: 11617 AN XY: 67148

Gnomad4 AFR AF: 0.0428

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.274

Gnomad4 EAS AF: 0.124

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.243

Gnomad4 NFE AF: 0.233

Gnomad4 OTH AF: 0.196

Alfa AF: 0.0677 Hom.: 115

Bravo AF: 0.146

Asia WGS AF: 0.124 AC: 430 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.9
DANN	Benign	0.48

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: rs12363280; hg19: chr11-231980;