rs2253217

Variant names:

• chr6-13600227-T-C
• rs2253217
• NM_012241.5:c.742-607T>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.742-607T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 152,112 control chromosomes in the GnomAD database, including 7,412 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 0.31 (7412 hom., cov: 32)
• Consequence: SIRT5 NM_012241.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0400
• Publications: 9 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]

LOC105374938 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012241.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIRT5	NM_012241.5	MANE Select	c.742-607T>C		intron	N/A	NP_036373.1	Q9NXA8-1
	SIRT5	NM_001376798.1		c.742-607T>C		intron	N/A	NP_001363727.1	Q9NXA8-1
	SIRT5	NM_001376799.1		c.742-607T>C		intron	N/A	NP_001363728.1	Q9NXA8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIRT5	ENST00000606117.2	TSL:1 MANE Select	c.742-607T>C		intron	N/A	ENSP00000476228.1	Q9NXA8-1
	SIRT5	ENST00000397350.7	TSL:1	c.742-607T>C		intron	N/A	ENSP00000380509.3	Q9NXA8-1
	SIRT5	ENST00000379262.8	TSL:1	c.742-607T>C		intron	N/A	ENSP00000368564.4	Q9NXA8-2

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46353 AN: 151994 Hom.: 7395 Cov.: 32

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.0652

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.316

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

GnomAD4 genome AF: 0.305 AC: 46404 AN: 152112 Hom.: 7412 Cov.: 32 AF XY: 0.304 AC XY: 22622 AN XY: 74352

African (AFR) AF: 0.282 AC: 11686 AN: 41500

American (AMR) AF: 0.406 AC: 6208 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 1127 AN: 3470

East Asian (EAS) AF: 0.0648 AC: 336 AN: 5184

South Asian (SAS) AF: 0.258 AC: 1243 AN: 4822

European-Finnish (FIN) AF: 0.302 AC: 3193 AN: 10558

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.318 AC: 21653 AN: 67986

Other (OTH) AF: 0.318 AC: 670 AN: 2110

Alfa AF: 0.316 Hom.: 4104

Bravo AF: 0.308

Asia WGS AF: 0.208 AC: 725 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.1
DANN	Benign	0.47
PhyloP100		-0.040
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2253217;

hg19: chr6-13600459;