rs1023430

Variant names:

• chr11-224393-A-G
• rs1023430
• NM_012239.6:c.808-154T>C

Variant summary

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

The NM_012239.6(SIRT3):​c.808-154T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 152,232 control chromosomes in the GnomAD database, including 3,353 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 0.20 (3353 hom., cov: 32)
• Consequence: SIRT3 NM_012239.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.00
• Publications: 23 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIRT3	NM_012239.6	c.808-154T>C		intron_variant	Intron 4 of 6	ENST00000382743.9	NP_036371.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIRT3	ENST00000382743.9	c.808-154T>C		intron_variant	Intron 4 of 6	1	NM_012239.6	ENSP00000372191.4

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30903 AN: 152116 Hom.: 3351 Cov.: 32

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.289

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.203 AC: 30911 AN: 152232 Hom.: 3353 Cov.: 32 AF XY: 0.206 AC XY: 15356 AN XY: 74438

African (AFR) AF: 0.188 AC: 7810 AN: 41540

American (AMR) AF: 0.216 AC: 3307 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 635 AN: 3468

East Asian (EAS) AF: 0.288 AC: 1495 AN: 5184

South Asian (SAS) AF: 0.447 AC: 2156 AN: 4826

European-Finnish (FIN) AF: 0.151 AC: 1603 AN: 10608

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.196 AC: 13311 AN: 68006

Other (OTH) AF: 0.186 AC: 393 AN: 2108

Alfa AF: 0.201 Hom.: 6181

Bravo AF: 0.199

Asia WGS AF: 0.344 AC: 1193 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	8.7
DANN	Benign	0.73
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1023430; hg19: chr11-224393;