rs11246020

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_012239.6(SIRT3):​c.622G>T​(p.Val208Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V208I) has been classified as Benign.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SIRT3
NM_012239.6 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.829
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.04883623).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SIRT3NM_012239.6 linkuse as main transcriptc.622G>T p.Val208Phe missense_variant 3/7 ENST00000382743.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SIRT3ENST00000382743.9 linkuse as main transcriptc.622G>T p.Val208Phe missense_variant 3/71 NM_012239.6 A2Q9NTG7-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461888
Hom.:
0
Cov.:
34
AF XY:
0.00000138
AC XY:
1
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.089
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
0.22
DANN
Benign
0.84
DEOGEN2
Benign
0.092
T;.;T;.;.;T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.040
N
LIST_S2
Benign
0.56
T;T;T;T;T;T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.049
T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.28
N;.;.;.;.;.
MutationTaster
Benign
1.0
P;P;P;P;P
PrimateAI
Benign
0.24
T
PROVEAN
Benign
-0.31
N;N;N;N;N;N
REVEL
Benign
0.22
Sift
Benign
0.37
T;T;T;T;T;T
Sift4G
Benign
0.54
T;T;T;T;T;.
Polyphen
0.031
B;B;B;B;.;.
Vest4
0.16
MutPred
0.35
Gain of ubiquitination at K205 (P = 0.1222);.;.;Gain of ubiquitination at K205 (P = 0.1222);.;.;
MVP
0.076
MPC
0.26
ClinPred
0.095
T
GERP RS
-3.3
Varity_R
0.13
gMVP
0.79

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs11246020; hg19: chr11-233067; API