11-232598-C-T

Variant names:

• chr11-232598-C-T
• rs4980329
• NM_012239.6:c.706+385G>A

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+385G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,046 control chromosomes in the GnomAD database, including 2,346 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 0.16 (2346 hom., cov: 31)
• Consequence: SIRT3 NM_012239.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.684
• Publications: 18 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.21 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+385G>A		intron	N/A	NP_036371.1
	SIRT3	NM_001370310.1		c.706+385G>A		intron	N/A	NP_001357239.1
	SIRT3	NM_001370312.1		c.514+385G>A		intron	N/A	NP_001357241.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIRT3	ENST00000382743.9	TSL:1 MANE Select	c.706+385G>A		intron	N/A	ENSP00000372191.4
	SIRT3	ENST00000941617.1		c.706+385G>A		intron	N/A	ENSP00000611676.1
	SIRT3	ENST00000852931.1		c.706+385G>A		intron	N/A	ENSP00000522990.1

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23764 AN: 151926 Hom.: 2348 Cov.: 31

Gnomad AFR AF: 0.0390

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.156 AC: 23751 AN: 152046 Hom.: 2346 Cov.: 31 AF XY: 0.156 AC XY: 11614 AN XY: 74320

African (AFR) AF: 0.0390 AC: 1617 AN: 41484

American (AMR) AF: 0.153 AC: 2338 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 875 AN: 3468

East Asian (EAS) AF: 0.112 AC: 582 AN: 5182

South Asian (SAS) AF: 0.147 AC: 706 AN: 4812

European-Finnish (FIN) AF: 0.223 AC: 2358 AN: 10566

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.213 AC: 14484 AN: 67956

Other (OTH) AF: 0.181 AC: 381 AN: 2104

Alfa AF: 0.167 Hom.: 430

Bravo AF: 0.146

Asia WGS AF: 0.124 AC: 431 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.6
DANN	Benign	0.82
PhyloP100		-0.68
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: rs4980329; hg19: chr11-232598;