rs2253217

Positions:

• chr6-13600227-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIRT5	NM_012241.5	c.742-607T>C		intron_variant		ENST00000606117.2	NP_036373.1
LOC105374938	XR_007059460.1	n.2165-586A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIRT5	ENST00000606117.2	c.742-607T>C		intron_variant		1	NM_012241.5	ENSP00000476228	P1

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

Gnomad4 AFR AF: 0.282

Gnomad4 AMR AF: 0.406

Gnomad4 ASJ AF: 0.325

Gnomad4 EAS AF: 0.0648

Gnomad4 SAS AF: 0.258

Gnomad4 FIN AF: 0.302

Gnomad4 NFE AF: 0.318

Gnomad4 OTH AF: 0.318

Alfa AF: 0.319 Hom.: 2622

Bravo AF: 0.308

Asia WGS AF: 0.208 AC: 725 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2253217; hg19: chr6-13600459;