12-120312571-G-A
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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
NM_012240.3 missense
Scores
3
16
Clinical Significance
Conservation
PhyloP100: 5.57
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]
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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 | 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 | c.613G>A | p.Val205Ile | missense_variant | 3/4 | 1 | NM_012240.3 | P1 | |
SIRT4 | ENST00000537892.1 | n.180-13G>A | splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.00390 AC: 593AN: 152172Hom.: 12 Cov.: 32
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GnomAD3 exomes AF: 0.00315 AC: 791AN: 251456Hom.: 4 AF XY: 0.00344 AC XY: 467AN XY: 135904
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GnomAD4 exome AF: 0.00440 AC: 6435AN: 1461888Hom.: 19 Cov.: 34 AF XY: 0.00440 AC XY: 3201AN XY: 727242
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GnomAD4 genome AF: 0.00389 AC: 593AN: 152290Hom.: 12 Cov.: 32 AF XY: 0.00381 AC XY: 284AN XY: 74462
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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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MVP
MPC
ClinPred
T
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at