11-231980-C-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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 (NFE) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012239.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIRT3	NM_012239.6	MANE Select	c.706+1003G>C		intron	N/A	NP_036371.1	Q9NTG7-1
	SIRT3	NM_001370310.1		c.706+1003G>C		intron	N/A	NP_001357239.1
	SIRT3	NM_001370312.1		c.514+1003G>C		intron	N/A	NP_001357241.1	E9PN58

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIRT3	ENST00000382743.9	TSL:1 MANE Select	c.706+1003G>C		intron	N/A	ENSP00000372191.4	Q9NTG7-1
	SIRT3	ENST00000941617.1		c.706+1003G>C		intron	N/A	ENSP00000611676.1
	SIRT3	ENST00000852931.1		c.706+1003G>C		intron	N/A	ENSP00000522990.1

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

African (AFR) AF: 0.0428 AC: 1608 AN: 37614

American (AMR) AF: 0.168 AC: 2346 AN: 13944

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 873 AN: 3186

East Asian (EAS) AF: 0.124 AC: 584 AN: 4712

South Asian (SAS) AF: 0.191 AC: 703 AN: 3676

European-Finnish (FIN) AF: 0.243 AC: 2357 AN: 9708

Middle Eastern (MID) AF: 0.264 AC: 64 AN: 242

European-Non Finnish (NFE) AF: 0.233 AC: 14479 AN: 62024

Other (OTH) AF: 0.196 AC: 382 AN: 1952

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.9
DANN	Benign	0.48
PhyloP100		-0.090
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs12363280;

hg19: chr11-231980;