11-217140-T-C

Variant names:

• chr11-217140-T-C
• rs3825075
• NM_012239.6:c.1180-422A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012239.6(SIRT3):​c.1180-422A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.714 in 152,212 control chromosomes in the GnomAD database, including 39,425 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 (39425 hom., cov: 35)
• Consequence: SIRT3 NM_012239.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.319
• Publications: 24 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.779 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.1180-422A>G		intron	N/A	NP_036371.1	Q9NTG7-1
	SIRT3	NM_001370310.1		c.1234-422A>G		intron	N/A	NP_001357239.1
	SIRT3	NM_001370312.1		c.1042-422A>G		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.1180-422A>G		intron	N/A	ENSP00000372191.4	Q9NTG7-1
	SIRT3	ENST00000941617.1		c.1279-422A>G		intron	N/A	ENSP00000611676.1
	SIRT3	ENST00000852931.1		c.1234-422A>G		intron	N/A	ENSP00000522990.1

Frequencies

GnomAD3 genomes AF: 0.714 AC: 108641 AN: 152094 Hom.: 39402 Cov.: 35

Gnomad AFR AF: 0.786

Gnomad AMI AF: 0.718

Gnomad AMR AF: 0.636

Gnomad ASJ AF: 0.648

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.720

Gnomad FIN AF: 0.751

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.711

Gnomad OTH AF: 0.676

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

GnomAD4 genome AF: 0.714 AC: 108708 AN: 152212 Hom.: 39425 Cov.: 35 AF XY: 0.715 AC XY: 53181 AN XY: 74408

African (AFR) AF: 0.786 AC: 32660 AN: 41552

American (AMR) AF: 0.635 AC: 9708 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.648 AC: 2249 AN: 3470

East Asian (EAS) AF: 0.404 AC: 2090 AN: 5176

South Asian (SAS) AF: 0.720 AC: 3478 AN: 4830

European-Finnish (FIN) AF: 0.751 AC: 7947 AN: 10582

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.711 AC: 48320 AN: 68002

Other (OTH) AF: 0.672 AC: 1421 AN: 2116

Alfa AF: 0.704 Hom.: 16304

Bravo AF: 0.704

Asia WGS AF: 0.593 AC: 2067 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.7
DANN	Benign	0.63
PhyloP100		0.32
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: rs3825075; hg19: chr11-217140;