6-13591903-C-T

Variant names:

• chr6-13591903-C-T
• rs3734674
• NM_012241.5:c.475+9C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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	c.475+9C>T		intron_variant	Intron 5 of 9	ENST00000606117.2	NP_036373.1

Ensembl

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

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

GnomAD2 exomes AF: 0.302 AC: 74764 AN: 247802 AF XY: 0.306

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 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

African (AFR) AF: 0.126 AC: 4207 AN: 33336

American (AMR) AF: 0.355 AC: 15794 AN: 44430

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 7716 AN: 26010

East Asian (EAS) AF: 0.172 AC: 6795 AN: 39472

South Asian (SAS) AF: 0.300 AC: 25835 AN: 86000

European-Finnish (FIN) AF: 0.303 AC: 16129 AN: 53278

Middle Eastern (MID) AF: 0.391 AC: 2243 AN: 5738

European-Non Finnish (NFE) AF: 0.326 AC: 360417 AN: 1104734

Other (OTH) AF: 0.309 AC: 18502 AN: 59918

GnomAD4 genome AF: 0.267 AC: 40650 AN: 152090 Hom.: 6033 Cov.: 32 AF XY: 0.267 AC XY: 19861 AN XY: 74352

African (AFR) AF: 0.130 AC: 5417 AN: 41538

American (AMR) AF: 0.337 AC: 5140 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 1028 AN: 3472

East Asian (EAS) AF: 0.184 AC: 952 AN: 5170

South Asian (SAS) AF: 0.306 AC: 1472 AN: 4810

European-Finnish (FIN) AF: 0.300 AC: 3170 AN: 10584

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.327 AC: 22239 AN: 67930

Other (OTH) AF: 0.296 AC: 625 AN: 2108

Alfa AF: 0.280 Hom.: 3933

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
PhyloP100		0.14
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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