11-218640-G-A

Variant names:

• chr11-218640-G-A
• rs535716
• NM_012239.6:c.1179+192C>T

Variant summary

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

The NM_012239.6(SIRT3):​c.1179+192C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 1,059,424 control chromosomes in the GnomAD database, including 29,828 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 0.28 (7303 hom., cov: 32)
  • Exomes 𝑓: 0.21 (22525 hom.)
• Consequence: SIRT3 NM_012239.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0920
• Publications: 9 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.475 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.1179+192C>T		intron	N/A	NP_036371.1	Q9NTG7-1
	SIRT3	NM_001370310.1		c.1233+138C>T		intron	N/A	NP_001357239.1
	SIRT3	NM_001370312.1		c.1041+138C>T		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.1179+192C>T		intron	N/A	ENSP00000372191.4	Q9NTG7-1
	SIRT3	ENST00000941617.1		c.1278+138C>T		intron	N/A	ENSP00000611676.1
	SIRT3	ENST00000852931.1		c.1233+138C>T		intron	N/A	ENSP00000522990.1

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42523 AN: 151896 Hom.: 7287 Cov.: 32

Gnomad AFR AF: 0.480

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.00481

Gnomad SAS AF: 0.0806

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.244

GnomAD4 exome AF: 0.211 AC: 191020 AN: 907410 Hom.: 22525 AF XY: 0.205 AC XY: 92640 AN XY: 452626

African (AFR) AF: 0.476 AC: 9993 AN: 20984

American (AMR) AF: 0.242 AC: 5436 AN: 22438

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 1987 AN: 17016

East Asian (EAS) AF: 0.00169 AC: 56 AN: 33136

South Asian (SAS) AF: 0.0802 AC: 4595 AN: 57296

European-Finnish (FIN) AF: 0.284 AC: 8616 AN: 30384

Middle Eastern (MID) AF: 0.103 AC: 353 AN: 3420

European-Non Finnish (NFE) AF: 0.222 AC: 151631 AN: 681654

Other (OTH) AF: 0.203 AC: 8353 AN: 41082

GnomAD4 genome AF: 0.280 AC: 42591 AN: 152014 Hom.: 7303 Cov.: 32 AF XY: 0.278 AC XY: 20658 AN XY: 74308

African (AFR) AF: 0.480 AC: 19884 AN: 41410

American (AMR) AF: 0.216 AC: 3297 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 401 AN: 3464

East Asian (EAS) AF: 0.00463 AC: 24 AN: 5184

South Asian (SAS) AF: 0.0805 AC: 387 AN: 4810

European-Finnish (FIN) AF: 0.289 AC: 3054 AN: 10578

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.218 AC: 14833 AN: 67974

Other (OTH) AF: 0.242 AC: 510 AN: 2108

Alfa AF: 0.343 Hom.: 2350

Bravo AF: 0.287

Asia WGS AF: 0.0790 AC: 278 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.1
DANN	Benign	0.78
PhyloP100		-0.092
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: rs535716; hg19: chr11-218640;