Variant 12-120312571-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_012240.3(SIRT4):c.613G>A(p.Val205Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00435 in 1,614,178 control chromosomes in the GnomAD database, including 31 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0039 ( 12 hom., cov: 32)

Exomes 𝑓: 0.0044 ( 19 hom. )

Consequence

SIRT4
NM_012240.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.57

Variant links:

Genes affected

SIRT4 (HGNC:14932): (sirtuin 4) 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 IV of the sirtuin family. [provided by RefSeq, Jul 2008]

SIRT4 links:

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=0.0047763884).

BP6

Variant 12-120312571-G-A is Benign according to our data. Variant chr12-120312571-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2643396.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 12 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIRT4	NM_012240.3 linkuse as main transcript	c.613G>A	p.Val205Ile	missense_variant	3/4	ENST00000202967.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIRT4	ENST00000202967.4 linkuse as main transcript	c.613G>A	p.Val205Ile	missense_variant	3/4	1	NM_012240.3	P1
SIRT4	ENST00000537892.1 linkuse as main transcript	n.180-13G>A		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00390

AC:

593

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000748

Gnomad AMI

AF:

0.142

Gnomad AMR

AF:

0.000459

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00358

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00548

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00315

AC:

791

AN:

251456

Hom.:

AF XY:

0.00344

AC XY:

467

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.000984

Gnomad AMR exome

AF:

0.000607

Gnomad ASJ exome

AF:

0.000198

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00199

Gnomad FIN exome

AF:

0.00333

Gnomad NFE exome

AF:

0.00533

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.00440

AC:

6435

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00440

AC XY:

3201

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.000568

Gnomad4 AMR exome

AF:

0.000626

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00176

Gnomad4 FIN exome

AF:

0.00432

Gnomad4 NFE exome

AF:

0.00523

Gnomad4 OTH exome

AF:

0.00295

GnomAD4 genome

AF:

0.00389

AC:

593

AN:

152290

Hom.:

Cov.:

AF XY:

0.00381

AC XY:

284

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.000746

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00358

Gnomad4 NFE

AF:

0.00548

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00435

Hom.:

Bravo

AF:

0.00403

TwinsUK

AF:

0.00405

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.00419

AC:

ExAC

AF:

0.00370

AC:

449

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00447

EpiControl

AF:

0.00427

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

SIRT4: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.090

Eigen

Benign

0.14

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.85

M_CAP

Benign

0.0079

MetaRNN

Benign

0.0048

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

MutationTaster

Benign

1.0

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.89

REVEL

Benign

0.088

Sift

Benign

0.085

Sift4G

Benign

0.10

Polyphen

0.090

Vest4

0.14

MVP

0.30

MPC

0.26

ClinPred

0.013

GERP RS

4.5

Varity_R

0.12

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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