6-13591903-C-T

Position:

• chr6-13591903-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.139

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]

ACMG classification

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/exons	MANE	UniProt
SIRT5	NM_012241.5	c.475+9C>T		intron_variant		ENST00000606117.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIRT5	ENST00000606117.2	c.475+9C>T		intron_variant		1	NM_012241.5	P1

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40626 AN: 151972 Hom.: 6029 Cov.: 32

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

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.: 32 AF XY: 0.316 AC XY: 227953 AN XY: 721076

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.: 32 AF XY: 0.267 AC XY: 19861 AN XY: 74352

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

Other links and lift over

dbSNP: rs3734674; hg19: chr6-13592135; COSMIC: COSV63082180; COSMIC: COSV63082180;