11-219089-T-C

Variant names:

• chr11-219089-T-C
• rs511744
• NM_012239.6:c.970-48A>G

Variant summary

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

The NM_012239.6(SIRT3):​c.970-48A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.705 in 1,550,270 control chromosomes in the GnomAD database, including 387,064 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 0.71 (38501 hom., cov: 31)
  • Exomes 𝑓: 0.70 (348563 hom.)
• Consequence: SIRT3 NM_012239.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0220
• Publications: 39 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.749 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.970-48A>G		intron	N/A	NP_036371.1	Q9NTG7-1
	SIRT3	NM_001370310.1		c.970-48A>G		intron	N/A	NP_001357239.1
	SIRT3	NM_001370312.1		c.778-48A>G		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.970-48A>G		intron	N/A	ENSP00000372191.4	Q9NTG7-1
	SIRT3	ENST00000941617.1		c.1015-48A>G		intron	N/A	ENSP00000611676.1
	SIRT3	ENST00000852931.1		c.970-48A>G		intron	N/A	ENSP00000522990.1

Frequencies

GnomAD3 genomes AF: 0.708 AC: 107577 AN: 151880 Hom.: 38471 Cov.: 31

Gnomad AFR AF: 0.756

Gnomad AMI AF: 0.719

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.648

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.722

Gnomad FIN AF: 0.740

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.706

Gnomad OTH AF: 0.679

GnomAD2 exomes AF: 0.681 AC: 116742 AN: 171356 AF XY: 0.684

Gnomad AFR exome AF: 0.753

Gnomad AMR exome AF: 0.626

Gnomad ASJ exome AF: 0.666

Gnomad EAS exome AF: 0.451

Gnomad FIN exome AF: 0.740

Gnomad NFE exome AF: 0.707

Gnomad OTH exome AF: 0.682

GnomAD4 exome AF: 0.705 AC: 985304 AN: 1398272 Hom.: 348563 Cov.: 39 AF XY: 0.705 AC XY: 485408 AN XY: 688788

African (AFR) AF: 0.761 AC: 24174 AN: 31752

American (AMR) AF: 0.632 AC: 23322 AN: 36886

Ashkenazi Jewish (ASJ) AF: 0.651 AC: 15838 AN: 24344

East Asian (EAS) AF: 0.483 AC: 17507 AN: 36276

South Asian (SAS) AF: 0.718 AC: 57081 AN: 79456

European-Finnish (FIN) AF: 0.736 AC: 36506 AN: 49608

Middle Eastern (MID) AF: 0.656 AC: 2708 AN: 4126

European-Non Finnish (NFE) AF: 0.713 AC: 768233 AN: 1078050

Other (OTH) AF: 0.691 AC: 39935 AN: 57774

GnomAD4 genome AF: 0.708 AC: 107656 AN: 151998 Hom.: 38501 Cov.: 31 AF XY: 0.709 AC XY: 52654 AN XY: 74306

African (AFR) AF: 0.756 AC: 31336 AN: 41442

American (AMR) AF: 0.659 AC: 10062 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.648 AC: 2249 AN: 3472

East Asian (EAS) AF: 0.477 AC: 2449 AN: 5138

South Asian (SAS) AF: 0.722 AC: 3477 AN: 4814

European-Finnish (FIN) AF: 0.740 AC: 7825 AN: 10574

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.706 AC: 48007 AN: 67980

Other (OTH) AF: 0.675 AC: 1422 AN: 2108

Alfa AF: 0.700 Hom.: 70366

Bravo AF: 0.703

Asia WGS AF: 0.633 AC: 2203 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	6.0
DANN	Benign	0.49
PhyloP100		-0.022
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: rs511744; hg19: chr11-219089; COSMIC: COSV57342795; COSMIC: COSV57342795;