6-13584199-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_012241.5(SIRT5):​c.89G>T​(p.Cys30Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,132 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

SIRT5
NM_012241.5 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.51
Variant links:
Genes affected
SIRT5 (HGNC:14933): (sirtuin 5) 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 III of the sirtuin family. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2010]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.17424148).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SIRT5NM_012241.5 linkuse as main transcriptc.89G>T p.Cys30Phe missense_variant 3/10 ENST00000606117.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SIRT5ENST00000606117.2 linkuse as main transcriptc.89G>T p.Cys30Phe missense_variant 3/101 NM_012241.5 P1Q9NXA8-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152132
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
30
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152132
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74316
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsFeb 28, 2024The c.89G>T (p.C30F) alteration is located in exon 3 (coding exon 1) of the SIRT5 gene. This alteration results from a G to T substitution at nucleotide position 89, causing the cysteine (C) at amino acid position 30 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.089
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
14
DANN
Benign
0.96
DEOGEN2
Benign
0.14
.;.;T
Eigen
Benign
-0.22
Eigen_PC
Benign
-0.23
FATHMM_MKL
Benign
0.70
D
LIST_S2
Benign
0.60
T;T;T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.17
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.8
M;M;M
MutationTaster
Benign
1.0
D;N;N;N
PrimateAI
Benign
0.45
T
PROVEAN
Benign
-1.2
N;N;.
REVEL
Benign
0.045
Sift
Benign
0.22
T;T;.
Sift4G
Benign
0.19
T;T;T
Polyphen
0.54, 0.40
.;P;B
Vest4
0.35
MutPred
0.36
Gain of MoRF binding (P = 0.0775);Gain of MoRF binding (P = 0.0775);Gain of MoRF binding (P = 0.0775);
MVP
0.47
MPC
0.16
ClinPred
0.44
T
GERP RS
3.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.085
gMVP
0.49

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.

Other links and lift over

dbSNP: rs1413919419; hg19: chr6-13584431; COSMIC: COSV63079928; COSMIC: COSV63079928; API