NM_012239.6:c.808-593A>C

Variant names:

• chr11-224832-T-G
• rs7934919
• NM_012239.6:c.808-593A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_012239.6(SIRT3):​c.808-593A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: SIRT3 NM_012239.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.705
• Publications: 10 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

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.808-593A>C		intron	N/A	NP_036371.1	Q9NTG7-1
	SIRT3	NM_001370310.1		c.808-593A>C		intron	N/A	NP_001357239.1
	SIRT3	NM_001370312.1		c.616-593A>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.808-593A>C		intron	N/A	ENSP00000372191.4	Q9NTG7-1
	SIRT3	ENST00000941617.1		c.808-548A>C		intron	N/A	ENSP00000611676.1
	SIRT3	ENST00000852931.1		c.808-593A>C		intron	N/A	ENSP00000522990.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1632

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.7
DANN	Benign	0.51
PhyloP100		-0.70

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: rs7934919; hg19: chr11-224832;