Genetic Variant SIRT5:c.115+126A>G (chr6-13584351-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.00

Publications

7 publications found

Variant links:

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 links:

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ACMG classification

Classification was made for transcript

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 = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIRT5	NM_012241.5 link	c.115+126A>G		intron_variant	Intron 3 of 9	ENST00000606117.2	NP_036373.1	Q9NXA8-1A0A024R012

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIRT5	ENST00000606117.2 link	c.115+126A>G		intron_variant	Intron 3 of 9	1	NM_012241.5	ENSP00000476228.1		Q9NXA8-1

Frequencies

GnomAD3 genomes

AF:

0.598

AC:

90616

AN:

151560

Hom.:

27330

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.576

AC:

7491

AN:

12994

American (AMR)

AF:

0.734

AC:

17817

AN:

24268

Ashkenazi Jewish (ASJ)

AF:

0.528

AC:

8489

AN:

16084

East Asian (EAS)

AF:

0.326

AC:

10148

AN:

31104

South Asian (SAS)

AF:

0.612

AC:

30908

AN:

50522

European-Finnish (FIN)

AF:

0.602

AC:

20071

AN:

33344

Middle Eastern (MID)

AF:

0.665

AC:

2480

AN:

3732

European-Non Finnish (NFE)

AF:

0.601

AC:

189128

AN:

314566

Other (OTH)

AF:

0.592

AC:

16701

AN:

28202

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

5509

11018

16528

22037

27546

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1380

2760

4140

5520

6900

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.598

AC:

90731

AN:

151676

Hom.:

27383

Cov.:

AF XY:

0.598

AC XY:

44304

AN XY:

74122

show subpopulations

African (AFR)

AF:

0.576

AC:

23832

AN:

41376

American (AMR)

AF:

0.681

AC:

10401

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.534

AC:

1854

AN:

3472

East Asian (EAS)

AF:

0.335

AC:

1725

AN:

5150

South Asian (SAS)

AF:

0.617

AC:

2968

AN:

4812

European-Finnish (FIN)

AF:

0.613

AC:

6395

AN:

10438

Middle Eastern (MID)

AF:

0.586

AC:

171

AN:

292

European-Non Finnish (NFE)

AF:

0.610

AC:

41386

AN:

67860

Other (OTH)

AF:

0.617

AC:

1299

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1854

3708

5562

7416

9270

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

760

1520

2280

3040

3800

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.599

Hom.:

80885

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

(source)

DANN

Benign

0.48

PhyloP100

-3.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over