Variant rs548590752 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_012238.5(SIRT1):c.110C>T(p.Pro37Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00317 in 1,223,802 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0029 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0032 ( 4 hom. )

Consequence

SIRT1
NM_012238.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

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]

SIRT1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008982778).

BP6

Variant 10-67884831-C-T is Benign according to our data. Variant chr10-67884831-C-T is described in ClinVar as [Benign]. Clinvar id is 1541459.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 443 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIRT1	NM_012238.5 link	c.110C>T	p.Pro37Leu	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
SIRT1	ENST00000212015.11 link	c.110C>T	p.Pro37Leu	missense_variant	Exon 1 of 9	1	NM_012238.5	ENSP00000212015.6		Q96EB6-1

Frequencies

GnomAD3 genomes

AF:

0.00293

AC:

444

AN:

151296

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000485

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.000392

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00894

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00427

Gnomad OTH

AF:

0.00289

GnomAD4 exome

AF:

0.00320

AC:

3436

AN:

1072400

Hom.:

Cov.:

AF XY:

0.00324

AC XY:

1641

AN XY:

506310

show subpopulations

Gnomad4 AFR exome

AF:

0.000398

Gnomad4 AMR exome

AF:

0.00123

Gnomad4 ASJ exome

AF:

0.00121

Gnomad4 EAS exome

AF:

0.000153

Gnomad4 SAS exome

AF:

0.00206

Gnomad4 FIN exome

AF:

0.00789

Gnomad4 NFE exome

AF:

0.00337

Gnomad4 OTH exome

AF:

0.00227

GnomAD4 genome

AF:

0.00293

AC:

443

AN:

151402

Hom.:

Cov.:

AF XY:

0.00309

AC XY:

229

AN XY:

74024

show subpopulations

Gnomad4 AFR

AF:

0.000483

Gnomad4 AMR

AF:

0.00164

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.000394

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00894

Gnomad4 NFE

AF:

0.00427

Gnomad4 OTH

AF:

0.00286

Alfa

AF:

0.00519

Hom.:

Bravo

AF:

0.00217

ExAC

AF:

0.000778

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 28, 2025	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

SIRT1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 11, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.20

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.59

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.0090

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

0.11

REVEL

Benign

0.076

Sift

Uncertain

0.0050

Sift4G

Benign

0.33

Polyphen

0.013

Vest4

0.15

MVP

0.24

MPC

0.69

ClinPred

0.63

GERP RS

0.55

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.044

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over