NM_012241.5:c.857+347T>C

Variant names:

• chr6-13601296-T-C
• rs2841514
• NM_012241.5:c.857+347T>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.857+347T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 152,018 control chromosomes in the GnomAD database, including 22,042 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 0.53 (22042 hom., cov: 32)
• Consequence: SIRT5 NM_012241.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.66
• Publications: 4 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.612 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.857+347T>C		intron	N/A	NP_036373.1	Q9NXA8-1
	SIRT5	NM_001376798.1		c.857+347T>C		intron	N/A	NP_001363727.1	Q9NXA8-1
	SIRT5	NM_001376799.1		c.857+347T>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.857+347T>C		intron	N/A	ENSP00000476228.1	Q9NXA8-1
	SIRT5	ENST00000397350.7	TSL:1	c.857+347T>C		intron	N/A	ENSP00000380509.3	Q9NXA8-1
	SIRT5	ENST00000379262.8	TSL:1	c.857+347T>C		intron	N/A	ENSP00000368564.4	Q9NXA8-2

Frequencies

GnomAD3 genomes AF: 0.533 AC: 80938 AN: 151900 Hom.: 22002 Cov.: 32

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.684

Gnomad AMR AF: 0.622

Gnomad ASJ AF: 0.557

Gnomad EAS AF: 0.246

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.536

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.566

Gnomad OTH AF: 0.562

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

GnomAD4 genome AF: 0.533 AC: 81033 AN: 152018 Hom.: 22042 Cov.: 32 AF XY: 0.531 AC XY: 39418 AN XY: 74302

African (AFR) AF: 0.480 AC: 19878 AN: 41450

American (AMR) AF: 0.622 AC: 9507 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.557 AC: 1934 AN: 3470

East Asian (EAS) AF: 0.246 AC: 1272 AN: 5174

South Asian (SAS) AF: 0.491 AC: 2369 AN: 4820

European-Finnish (FIN) AF: 0.536 AC: 5656 AN: 10556

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

European-Non Finnish (NFE) AF: 0.566 AC: 38447 AN: 67948

Other (OTH) AF: 0.561 AC: 1187 AN: 2114

Alfa AF: 0.564 Hom.: 30785

Bravo AF: 0.533

Asia WGS AF: 0.418 AC: 1455 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.0010
DANN	Benign	0.18
PhyloP100		-2.7
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: rs2841514; hg19: chr6-13601528;