rs11751539

Variant names:

• chr6-13598324-A-T
• rs11751539
• NM_012241.5:c.618-708A>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.618-708A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0892 in 152,192 control chromosomes in the GnomAD database, including 1,048 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 0.089 (1048 hom., cov: 31)
• Consequence: SIRT5 NM_012241.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIRT5	NM_012241.5	c.618-708A>T		intron_variant	Intron 7 of 9	ENST00000606117.2	NP_036373.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIRT5	ENST00000606117.2	c.618-708A>T		intron_variant	Intron 7 of 9	1	NM_012241.5	ENSP00000476228.1

Frequencies

GnomAD3 genomes AF: 0.0892 AC: 13564 AN: 152074 Hom.: 1045 Cov.: 31

Gnomad AFR AF: 0.0204

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.0732

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.0845

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0980

Gnomad OTH AF: 0.0918

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

GnomAD4 genome AF: 0.0892 AC: 13568 AN: 152192 Hom.: 1048 Cov.: 31 AF XY: 0.0911 AC XY: 6781 AN XY: 74398

African (AFR) AF: 0.0203 AC: 843 AN: 41556

American (AMR) AF: 0.109 AC: 1662 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0732 AC: 254 AN: 3472

East Asian (EAS) AF: 0.423 AC: 2180 AN: 5152

South Asian (SAS) AF: 0.0844 AC: 407 AN: 4824

European-Finnish (FIN) AF: 0.125 AC: 1320 AN: 10592

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0980 AC: 6663 AN: 67986

Other (OTH) AF: 0.0956 AC: 202 AN: 2114

Alfa AF: 0.0958 Hom.: 100

Bravo AF: 0.0886

Asia WGS AF: 0.212 AC: 736 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.12
DANN	Benign	0.51
PhyloP100		-1.4
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: rs11751539; hg19: chr6-13598556;