Genetic Variant SIRT5:c.475+9C>T (chr6-13591903-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_012241.5(SIRT5):c.475+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 1,605,006 control chromosomes in the GnomAD database, including 79,807 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.27 ( 6033 hom., cov: 32)

Exomes 𝑓: 0.31 ( 73774 hom. )

Consequence

SIRT5
NM_012241.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.139

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]

SIRT5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIRT5	NM_012241.5 link	c.475+9C>T		intron_variant	Intron 5 of 9	ENST00000606117.2	NP_036373.1	Q9NXA8-1A0A024R012

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIRT5	ENST00000606117.2 link	c.475+9C>T		intron_variant	Intron 5 of 9	1	NM_012241.5	ENSP00000476228.1		Q9NXA8-1

Frequencies

GnomAD3 genomes

AF:

0.267

AC:

40626

AN:

151972

Hom.:

6029

Cov.:

show subpopulations

Gnomad AFR

AF:

0.130

Gnomad AMI

AF:

0.565

Gnomad AMR

AF:

0.337

Gnomad ASJ

AF:

0.296

Gnomad EAS

AF:

0.184

Gnomad SAS

AF:

0.305

Gnomad FIN

AF:

0.300

Gnomad MID

AF:

0.304

Gnomad NFE

AF:

0.327

Gnomad OTH

AF:

0.298

GnomAD3 exomes

AF:

0.302

AC:

74764

AN:

247802

Hom.:

11744

AF XY:

0.306

AC XY:

41060

AN XY:

134094

show subpopulations

Gnomad AFR exome

AF:

0.125

Gnomad AMR exome

AF:

0.357

Gnomad ASJ exome

AF:

0.294

Gnomad EAS exome

AF:

0.177

Gnomad SAS exome

AF:

0.302

Gnomad FIN exome

AF:

0.301

Gnomad NFE exome

AF:

0.329

Gnomad OTH exome

AF:

0.334

GnomAD4 exome

AF:

0.315

AC:

457638

AN:

1452916

Hom.:

73774

Cov.:

AF XY:

0.316

AC XY:

227953

AN XY:

721076

show subpopulations

Gnomad4 AFR exome

AF:

0.126

Gnomad4 AMR exome

AF:

0.355

Gnomad4 ASJ exome

AF:

0.297

Gnomad4 EAS exome

AF:

0.172

Gnomad4 SAS exome

AF:

0.300

Gnomad4 FIN exome

AF:

0.303

Gnomad4 NFE exome

AF:

0.326

Gnomad4 OTH exome

AF:

0.309

GnomAD4 genome

AF:

0.267

AC:

40650

AN:

152090

Hom.:

6033

Cov.:

AF XY:

0.267

AC XY:

19861

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.130

Gnomad4 AMR

AF:

0.337

Gnomad4 ASJ

AF:

0.296

Gnomad4 EAS

AF:

0.184

Gnomad4 SAS

AF:

0.306

Gnomad4 FIN

AF:

0.300

Gnomad4 NFE

AF:

0.327

Gnomad4 OTH

AF:

0.296

Alfa

AF:

0.278

Hom.:

3381

Bravo

AF:

0.262

Asia WGS

AF:

0.241

AC:

838

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

6.0

DANN

Benign

0.70

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over