chr11-230751-A-G

Variant names:

• chr11-230751-A-G
• rs3829998
• NM_012239.6:c.707-199T>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.707-199T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.771 in 388,890 control chromosomes in the GnomAD database, including 116,350 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 0.79 (48163 hom., cov: 32)
  • Exomes 𝑓: 0.76 (68187 hom.)
• Consequence: SIRT3 NM_012239.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.508
• Publications: 11 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIRT3	NM_012239.6	c.707-199T>C		intron_variant	Intron 3 of 6	ENST00000382743.9	NP_036371.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIRT3	ENST00000382743.9	c.707-199T>C		intron_variant	Intron 3 of 6	1	NM_012239.6	ENSP00000372191.4

Frequencies

GnomAD3 genomes AF: 0.793 AC: 120506 AN: 152034 Hom.: 48111 Cov.: 32

Gnomad AFR AF: 0.891

Gnomad AMI AF: 0.731

Gnomad AMR AF: 0.806

Gnomad ASJ AF: 0.670

Gnomad EAS AF: 0.827

Gnomad SAS AF: 0.797

Gnomad FIN AF: 0.765

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.740

Gnomad OTH AF: 0.761

GnomAD4 exome AF: 0.757 AC: 179218 AN: 236738 Hom.: 68187 Cov.: 3 AF XY: 0.754 AC XY: 90770 AN XY: 120396

African (AFR) AF: 0.883 AC: 6075 AN: 6878

American (AMR) AF: 0.821 AC: 5759 AN: 7012

Ashkenazi Jewish (ASJ) AF: 0.678 AC: 6040 AN: 8906

East Asian (EAS) AF: 0.842 AC: 18315 AN: 21762

South Asian (SAS) AF: 0.788 AC: 2663 AN: 3380

European-Finnish (FIN) AF: 0.761 AC: 15219 AN: 20002

Middle Eastern (MID) AF: 0.717 AC: 889 AN: 1240

European-Non Finnish (NFE) AF: 0.740 AC: 112446 AN: 151994

Other (OTH) AF: 0.759 AC: 11812 AN: 15564

GnomAD4 genome AF: 0.793 AC: 120611 AN: 152152 Hom.: 48163 Cov.: 32 AF XY: 0.796 AC XY: 59175 AN XY: 74378

African (AFR) AF: 0.891 AC: 36982 AN: 41518

American (AMR) AF: 0.807 AC: 12326 AN: 15280

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

East Asian (EAS) AF: 0.827 AC: 4276 AN: 5168

South Asian (SAS) AF: 0.797 AC: 3845 AN: 4824

European-Finnish (FIN) AF: 0.765 AC: 8088 AN: 10576

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.740 AC: 50313 AN: 67996

Other (OTH) AF: 0.757 AC: 1598 AN: 2112

Alfa AF: 0.714 Hom.: 2337

Bravo AF: 0.801

Asia WGS AF: 0.806 AC: 2805 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.87
DANN	Benign	0.31
PhyloP100		-0.51
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3829998; hg19: chr11-230751;