6-13584351-A-G

Position:

• chr6-13584351-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012241.5(SIRT5):​c.115+126A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 666,492 control chromosomes in the GnomAD database, including 120,203 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 0.60 (27383 hom., cov: 31)
  • Exomes 𝑓: 0.59 (92820 hom.)
• Consequence: SIRT5 NM_012241.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.00

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]

SIRT5 (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 = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIRT5	NM_012241.5	c.115+126A>G		intron_variant		ENST00000606117.2	NP_036373.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIRT5	ENST00000606117.2	c.115+126A>G		intron_variant		1	NM_012241.5	ENSP00000476228.1

Frequencies

GnomAD3 genomes AF: 0.598 AC: 90616 AN: 151560 Hom.: 27330 Cov.: 31

Gnomad AFR AF: 0.575

Gnomad AMI AF: 0.769

Gnomad AMR AF: 0.681

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.616

Gnomad FIN AF: 0.613

Gnomad MID AF: 0.596

Gnomad NFE AF: 0.610

Gnomad OTH AF: 0.618

GnomAD4 exome AF: 0.589 AC: 303233 AN: 514816 Hom.: 92820 AF XY: 0.591 AC XY: 162553 AN XY: 275246

Gnomad4 AFR exome AF: 0.576

Gnomad4 AMR exome AF: 0.734

Gnomad4 ASJ exome AF: 0.528

Gnomad4 EAS exome AF: 0.326

Gnomad4 SAS exome AF: 0.612

Gnomad4 FIN exome AF: 0.602

Gnomad4 NFE exome AF: 0.601

Gnomad4 OTH exome AF: 0.592

GnomAD4 genome AF: 0.598 AC: 90731 AN: 151676 Hom.: 27383 Cov.: 31 AF XY: 0.598 AC XY: 44304 AN XY: 74122

Gnomad4 AFR AF: 0.576

Gnomad4 AMR AF: 0.681

Gnomad4 ASJ AF: 0.534

Gnomad4 EAS AF: 0.335

Gnomad4 SAS AF: 0.617

Gnomad4 FIN AF: 0.613

Gnomad4 NFE AF: 0.610

Gnomad4 OTH AF: 0.617

Alfa AF: 0.597 Hom.: 49450

Bravo AF: 0.597

Asia WGS AF: 0.523 AC: 1818 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.48
DANN	Benign	0.48

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: rs2804918; hg19: chr6-13584583; COSMIC: COSV63080725;