NM_012239.6:c.1180-422A>G

Variant names:

• chr11-217140-T-C
• rs3825075
• NM_012239.6:c.1180-422A>G

Variant summary

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

The NM_012239.6(SIRT3):​c.1180-422A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.714 in 152,212 control chromosomes in the GnomAD database, including 39,425 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 (39425 hom., cov: 35)
• Consequence: SIRT3 NM_012239.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.319

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIRT3	NM_012239.6	c.1180-422A>G		intron_variant	Intron 6 of 6	ENST00000382743.9	NP_036371.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIRT3	ENST00000382743.9	c.1180-422A>G		intron_variant	Intron 6 of 6	1	NM_012239.6	ENSP00000372191.4

Frequencies

GnomAD3 genomes AF: 0.714 AC: 108641 AN: 152094 Hom.: 39402 Cov.: 35

Gnomad AFR AF: 0.786

Gnomad AMI AF: 0.718

Gnomad AMR AF: 0.636

Gnomad ASJ AF: 0.648

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.720

Gnomad FIN AF: 0.751

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.711

Gnomad OTH AF: 0.676

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

GnomAD4 genome AF: 0.714 AC: 108708 AN: 152212 Hom.: 39425 Cov.: 35 AF XY: 0.715 AC XY: 53181 AN XY: 74408

Gnomad4 AFR AF: 0.786

Gnomad4 AMR AF: 0.635

Gnomad4 ASJ AF: 0.648

Gnomad4 EAS AF: 0.404

Gnomad4 SAS AF: 0.720

Gnomad4 FIN AF: 0.751

Gnomad4 NFE AF: 0.711

Gnomad4 OTH AF: 0.672

Alfa AF: 0.701 Hom.: 13186

Bravo AF: 0.704

Asia WGS AF: 0.593 AC: 2067 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.7
DANN	Benign	0.63

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: rs3825075; hg19: chr11-217140;