rs2804916

Variant names:

• chr6-13581612-T-C
• rs2804916
• NM_012241.5:c.-36+2003T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012241.5(SIRT5):​c.-36+2003T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 152,162 control chromosomes in the GnomAD database, including 6,544 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 0.29 (6544 hom., cov: 32)
• Consequence: SIRT5 NM_012241.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0290
• Publications: 14 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIRT5	NM_012241.5	c.-36+2003T>C		intron_variant	Intron 2 of 9	ENST00000606117.2	NP_036373.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIRT5	ENST00000606117.2	c.-36+2003T>C		intron_variant	Intron 2 of 9	1	NM_012241.5	ENSP00000476228.1

Frequencies

GnomAD3 genomes AF: 0.290 AC: 44052 AN: 152044 Hom.: 6539 Cov.: 32

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.293

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

GnomAD4 genome AF: 0.290 AC: 44082 AN: 152162 Hom.: 6544 Cov.: 32 AF XY: 0.291 AC XY: 21661 AN XY: 74392

African (AFR) AF: 0.255 AC: 10596 AN: 41506

American (AMR) AF: 0.326 AC: 4983 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.262 AC: 909 AN: 3472

East Asian (EAS) AF: 0.122 AC: 633 AN: 5180

South Asian (SAS) AF: 0.312 AC: 1501 AN: 4818

European-Finnish (FIN) AF: 0.330 AC: 3493 AN: 10586

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.311 AC: 21139 AN: 67996

Other (OTH) AF: 0.294 AC: 621 AN: 2110

Alfa AF: 0.305 Hom.: 1491

Bravo AF: 0.283

Asia WGS AF: 0.251 AC: 872 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
DANN	Benign	0.73
PhyloP100		-0.029
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: rs2804916; hg19: chr6-13581844;