chr11-233212-C-G

Variant names:

• chr11-233212-C-G
• rs11555236
• NM_012239.6:c.477G>C

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_012239.6(SIRT3):​c.477G>C​(p.Ser159Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,460,406 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S159S) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: SIRT3 NM_012239.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.384
• Publications: 34 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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP7: Synonymous conserved (PhyloP=0.384 with no splicing effect.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIRT3	NM_012239.6	MANE Select	c.477G>C	p.Ser159Ser	synonymous	Exon 3 of 7	NP_036371.1
	SIRT3	NM_001370310.1		c.477G>C	p.Ser159Ser	synonymous	Exon 3 of 7	NP_001357239.1
	SIRT3	NM_001370312.1		c.285G>C	p.Ser95Ser	synonymous	Exon 2 of 6	NP_001357241.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIRT3	ENST00000382743.9	TSL:1 MANE Select	c.477G>C	p.Ser159Ser	synonymous	Exon 3 of 7	ENSP00000372191.4
	SIRT3	ENST00000524564.5	TSL:2	c.285G>C	p.Ser95Ser	synonymous	Exon 2 of 6	ENSP00000432937.1
	SIRT3	ENST00000532956.5	TSL:2	c.477G>C	p.Ser159Ser	synonymous	Exon 3 of 6	ENSP00000433077.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000160 AC: 4 AN: 250078 AF XY: 0.00000740

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1460406 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726298

African (AFR) AF: 0.00 AC: 0 AN: 33388

American (AMR) AF: 0.000135 AC: 6 AN: 44582

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26070

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.00 AC: 0 AN: 86214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111006

Other (OTH) AF: 0.00 AC: 0 AN: 60310

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 1870

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	17
DANN	Benign	0.64
PhyloP100		0.38
PromoterAI		-0.082	Neutral

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: rs11555236; hg19: chr11-233212;