rs6598074

Variant names:

• chr11-219398-G-A
• rs6598074
• NM_012239.6:c.970-357C>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.970-357C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.81 in 152,086 control chromosomes in the GnomAD database, including 50,564 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 0.81 (50564 hom., cov: 31)
• Consequence: SIRT3 NM_012239.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.230
• Publications: 8 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.942 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIRT3	NM_012239.6	c.970-357C>T		intron_variant	Intron 5 of 6	ENST00000382743.9	NP_036371.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIRT3	ENST00000382743.9	c.970-357C>T		intron_variant	Intron 5 of 6	1	NM_012239.6	ENSP00000372191.4

Frequencies

GnomAD3 genomes AF: 0.810 AC: 123075 AN: 151968 Hom.: 50504 Cov.: 31

Gnomad AFR AF: 0.950

Gnomad AMI AF: 0.731

Gnomad AMR AF: 0.815

Gnomad ASJ AF: 0.670

Gnomad EAS AF: 0.829

Gnomad SAS AF: 0.792

Gnomad FIN AF: 0.765

Gnomad MID AF: 0.657

Gnomad NFE AF: 0.740

Gnomad OTH AF: 0.772

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

GnomAD4 genome AF: 0.810 AC: 123189 AN: 152086 Hom.: 50564 Cov.: 31 AF XY: 0.812 AC XY: 60322 AN XY: 74324

African (AFR) AF: 0.950 AC: 39449 AN: 41514

American (AMR) AF: 0.816 AC: 12463 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.670 AC: 2325 AN: 3472

East Asian (EAS) AF: 0.829 AC: 4283 AN: 5164

South Asian (SAS) AF: 0.792 AC: 3811 AN: 4812

European-Finnish (FIN) AF: 0.765 AC: 8067 AN: 10550

Middle Eastern (MID) AF: 0.652 AC: 189 AN: 290

European-Non Finnish (NFE) AF: 0.740 AC: 50321 AN: 67990

Other (OTH) AF: 0.767 AC: 1614 AN: 2104

Alfa AF: 0.784 Hom.: 13647

Bravo AF: 0.822

Asia WGS AF: 0.809 AC: 2814 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.3
DANN	Benign	0.35
PhyloP100		0.23
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: rs6598074; hg19: chr11-219398;