rs4712047

Variant names:

• chr6-13589953-A-G
• rs4712047
• NM_012241.5:c.249+1489A>G

Variant summary

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

The NM_012241.5(SIRT5):​c.249+1489A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 151,698 control chromosomes in the GnomAD database, including 16,456 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 0.46 (16456 hom., cov: 31)
• Consequence: SIRT5 NM_012241.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0280
• Publications: 15 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIRT5	NM_012241.5	c.249+1489A>G		intron_variant	Intron 4 of 9	ENST00000606117.2	NP_036373.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIRT5	ENST00000606117.2	c.249+1489A>G		intron_variant	Intron 4 of 9	1	NM_012241.5	ENSP00000476228.1

Frequencies

GnomAD3 genomes AF: 0.460 AC: 69680 AN: 151580 Hom.: 16443 Cov.: 31

Gnomad AFR AF: 0.577

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.443

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

GnomAD4 genome AF: 0.460 AC: 69742 AN: 151698 Hom.: 16456 Cov.: 31 AF XY: 0.457 AC XY: 33859 AN XY: 74126

African (AFR) AF: 0.577 AC: 23856 AN: 41356

American (AMR) AF: 0.407 AC: 6194 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 1472 AN: 3468

East Asian (EAS) AF: 0.540 AC: 2780 AN: 5144

South Asian (SAS) AF: 0.471 AC: 2258 AN: 4792

European-Finnish (FIN) AF: 0.331 AC: 3473 AN: 10506

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.413 AC: 28052 AN: 67886

Other (OTH) AF: 0.442 AC: 929 AN: 2104

Alfa AF: 0.430 Hom.: 25673

Bravo AF: 0.473

Asia WGS AF: 0.477 AC: 1666 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.0
DANN	Benign	0.58
PhyloP100		-0.028
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: rs4712047; hg19: chr6-13590185;