12-120312571-G-A

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

3
16

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]

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
SIRT4NM_012240.3 linkuse as main transcriptc.613G>A p.Val205Ile missense_variant 3/4 ENST00000202967.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SIRT4ENST00000202967.4 linkuse as main transcriptc.613G>A p.Val205Ile missense_variant 3/41 NM_012240.3 P1
SIRT4ENST00000537892.1 linkuse as main transcriptn.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.:
12
Cov.:
32
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.:
4
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.:
19
Cov.:
34
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.:
12
Cov.:
32
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.:
1
Bravo
AF:
0.00403
TwinsUK
AF:
0.00405
AC:
15
ALSPAC
AF:
0.00311
AC:
12
ESP6500AA
AF:
0.00182
AC:
8
ESP6500EA
AF:
0.00419
AC:
36
ExAC
AF:
0.00370
AC:
449
Asia WGS
AF:
0.00173
AC:
6
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 submitterclinical testingCeGaT Center for Human Genetics TuebingenDec 01, 2022SIRT4: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.46
T
BayesDel_noAF
Benign
-0.43
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.090
T
Eigen
Benign
0.14
Eigen_PC
Uncertain
0.25
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.85
D
M_CAP
Benign
0.0079
T
MetaRNN
Benign
0.0048
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.2
L
MutationTaster
Benign
1.0
D
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-0.89
N
REVEL
Benign
0.088
Sift
Benign
0.085
T
Sift4G
Benign
0.10
T
Polyphen
0.090
B
Vest4
0.14
MVP
0.30
MPC
0.26
ClinPred
0.013
T
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.

Other links and lift over

dbSNP: rs150394622; hg19: chr12-120750374; API