11-232598-C-T

Position:

• chr11-232598-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000382743.9(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 ENST00000382743.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.684

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIRT3	NM_012239.6	c.706+385G>A		intron_variant		ENST00000382743.9	NP_036371.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIRT3	ENST00000382743.9	c.706+385G>A		intron_variant		1	NM_012239.6	ENSP00000372191	A2

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

Gnomad4 AFR AF: 0.0390

Gnomad4 AMR AF: 0.153

Gnomad4 ASJ AF: 0.252

Gnomad4 EAS AF: 0.112

Gnomad4 SAS AF: 0.147

Gnomad4 FIN AF: 0.223

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.181

Alfa AF: 0.171 Hom.: 429

Bravo AF: 0.146

Asia WGS AF: 0.124 AC: 431 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.6
DANN	Benign	0.82

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

Publications

LitVar

Other links and lift over

dbSNP: rs4980329; hg19: chr11-232598;