rs9382227

Variant names:

• chr6-13578852-G-T
• rs9382227
• NM_012241.5:c.-194-599G>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.-194-599G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 151,822 control chromosomes in the GnomAD database, including 5,442 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 0.26 (5442 hom., cov: 30)
• Consequence: SIRT5 NM_012241.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.567
• Publications: 5 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIRT5	NM_012241.5	c.-194-599G>T		intron_variant	Intron 1 of 9	ENST00000606117.2	NP_036373.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIRT5	ENST00000606117.2	c.-194-599G>T		intron_variant	Intron 1 of 9	1	NM_012241.5	ENSP00000476228.1

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39355 AN: 151704 Hom.: 5439 Cov.: 30

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.288

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.259 AC: 39386 AN: 151822 Hom.: 5442 Cov.: 30 AF XY: 0.259 AC XY: 19184 AN XY: 74168

African (AFR) AF: 0.157 AC: 6492 AN: 41424

American (AMR) AF: 0.333 AC: 5069 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 883 AN: 3470

East Asian (EAS) AF: 0.224 AC: 1157 AN: 5154

South Asian (SAS) AF: 0.303 AC: 1452 AN: 4796

European-Finnish (FIN) AF: 0.278 AC: 2918 AN: 10504

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.297 AC: 20160 AN: 67924

Other (OTH) AF: 0.286 AC: 605 AN: 2112

Alfa AF: 0.279 Hom.: 2879

Bravo AF: 0.259

Asia WGS AF: 0.258 AC: 898 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.62
DANN	Benign	0.38
PhyloP100		-0.57
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs9382227; hg19: chr6-13579084;