19-38883666-C-T
Position:
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_012237.4(SIRT2):c.592G>A(p.Ala198Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000711 in 1,614,114 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0038 ( 5 hom., cov: 31)
Exomes 𝑓: 0.00039 ( 1 hom. )
Consequence
SIRT2
NM_012237.4 missense
NM_012237.4 missense
Scores
12
Clinical Significance
Conservation
PhyloP100: -0.211
Genes affected
SIRT2 (HGNC:10886): (sirtuin 2) 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. Several transcript variants are resulted from alternative splicing of this gene. [provided by RefSeq, Jul 2010]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.0036205053).
BP6
Variant 19-38883666-C-T is Benign according to our data. Variant chr19-38883666-C-T is described in ClinVar as [Benign]. Clinvar id is 781449.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAd4 at 5 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SIRT2 | NM_012237.4 | c.592G>A | p.Ala198Thr | missense_variant | 9/16 | ENST00000249396.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SIRT2 | ENST00000249396.12 | c.592G>A | p.Ala198Thr | missense_variant | 9/16 | 1 | NM_012237.4 | P4 |
Frequencies
GnomAD3 genomes AF: 0.00375 AC: 571AN: 152208Hom.: 5 Cov.: 31
GnomAD3 genomes
AF:
AC:
571
AN:
152208
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000995 AC: 250AN: 251376Hom.: 2 AF XY: 0.000788 AC XY: 107AN XY: 135870
GnomAD3 exomes
AF:
AC:
250
AN:
251376
Hom.:
AF XY:
AC XY:
107
AN XY:
135870
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000392 AC: 573AN: 1461788Hom.: 1 Cov.: 31 AF XY: 0.000359 AC XY: 261AN XY: 727204
GnomAD4 exome
AF:
AC:
573
AN:
1461788
Hom.:
Cov.:
31
AF XY:
AC XY:
261
AN XY:
727204
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.00377 AC: 574AN: 152326Hom.: 5 Cov.: 31 AF XY: 0.00346 AC XY: 258AN XY: 74480
GnomAD4 genome
AF:
AC:
574
AN:
152326
Hom.:
Cov.:
31
AF XY:
AC XY:
258
AN XY:
74480
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ESP6500AA
AF:
AC:
46
ESP6500EA
AF:
AC:
0
ExAC
AF:
AC:
152
Asia WGS
AF:
AC:
1
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N
PrimateAI
Benign
T
REVEL
Benign
Polyphen
0.0010
.;B;B;.;.;.
Vest4
MVP
MPC
0.21
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at