rs548590752

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_012238.5(SIRT1):​c.110C>G​(p.Pro37Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Consequence

SIRT1
NM_012238.5 missense

Scores

1
3
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.369
Variant links:
Genes affected
SIRT1 (HGNC:14929): (sirtuin 1) This gene encodes a member of the sirtuin family of proteins, homologs to the yeast Sir2 protein. Members of the sirtuin family are characterized by a sirtuin core domain and grouped into four classes. The functions of human sirtuins have not yet been determined; however, yeast sirtuin proteins are known to regulate epigenetic gene silencing and suppress recombination of rDNA. Studies suggest that the human sirtuins may function as intracellular regulatory proteins with mono-ADP-ribosyltransferase activity. The protein encoded by this gene is included in class I of the sirtuin family. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.11004925).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SIRT1NM_012238.5 linkc.110C>G p.Pro37Arg missense_variant Exon 1 of 9 ENST00000212015.11 NP_036370.2 Q96EB6-1A0A024QZQ1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SIRT1ENST00000212015.11 linkc.110C>G p.Pro37Arg missense_variant Exon 1 of 9 1 NM_012238.5 ENSP00000212015.6 Q96EB6-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
34
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.082
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
21
DANN
Uncertain
0.98
DEOGEN2
Benign
0.25
T
Eigen
Benign
-0.61
Eigen_PC
Benign
-0.55
FATHMM_MKL
Benign
0.56
D
LIST_S2
Benign
0.51
T
M_CAP
Uncertain
0.099
D
MetaRNN
Benign
0.11
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.90
L
PrimateAI
Pathogenic
0.92
D
PROVEAN
Benign
-0.51
N
REVEL
Benign
0.060
Sift
Uncertain
0.0070
D
Sift4G
Benign
0.78
T
Polyphen
0.0060
B
Vest4
0.17
MutPred
0.27
Loss of glycosylation at P37 (P = 0.0113);
MVP
0.22
MPC
0.83
ClinPred
0.51
D
GERP RS
0.55
Varity_R
0.050
gMVP
0.28

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-69644589; API