dbSNP rs107251: SIRT6:c.438-151A>G (chr19-4176088-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_016539.4(SIRT6):c.438-151A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.873 in 624,604 control chromosomes in the GnomAD database, including 239,459 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 0.88 ( 59864 hom., cov: 31)

Exomes 𝑓: 0.87 ( 179595 hom. )

Consequence

SIRT6
NM_016539.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.47

Publications

42 publications found

Variant links:

Genes affected

SIRT6 (HGNC:14934): (sirtuin 6) This gene encodes a member of the sirtuin family of NAD-dependent enzymes that are implicated in cellular stress resistance, genomic stability, aging and energy homeostasis. The encoded protein is localized to the nucleus, exhibits ADP-ribosyl transferase and histone deacetylase activities, and plays a role in DNA repair, maintenance of telomeric chromatin, inflammation, lipid and glucose metabolism. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2016]

SIRT6 links:

Genome browser will be placed here

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=-1.03).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.945 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016539.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SIRT6	NM_016539.4	MANE Select	c.438-151A>G	intron	N/A	NP_057623.2
SIRT6	NM_001193285.3		c.438-151A>G	intron	N/A	NP_001180214.1
SIRT6	NM_001321059.2		c.255-151A>G	intron	N/A	NP_001307988.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SIRT6	ENST00000337491.7	TSL:1 MANE Select	c.438-151A>G	intron	N/A	ENSP00000337332.1
SIRT6	ENST00000305232.10	TSL:1	c.438-151A>G	intron	N/A	ENSP00000305310.5
SIRT6	ENST00000599365.5	TSL:1	n.*178-151A>G	intron	N/A	ENSP00000473085.1

Frequencies

GnomAD3 genomes

AF:

0.884

AC:

134417

AN:

152030

Hom.:

59820

Cov.:

show subpopulations

Gnomad AFR

AF:

0.953

Gnomad AMI

AF:

0.829

Gnomad AMR

AF:

0.775

Gnomad ASJ

AF:

0.866

Gnomad EAS

AF:

0.699

Gnomad SAS

AF:

0.911

Gnomad FIN

AF:

0.850

Gnomad MID

AF:

0.943

Gnomad NFE

AF:

0.885

Gnomad OTH

AF:

0.888

GnomAD4 exome

AF:

0.870

AC:

410842

AN:

472456

Hom.:

179595

AF XY:

0.874

AC XY:

216219

AN XY:

247390

show subpopulations

African (AFR)

AF:

0.955

AC:

12566

AN:

13156

American (AMR)

AF:

0.745

AC:

15708

AN:

21076

Ashkenazi Jewish (ASJ)

AF:

0.863

AC:

12149

AN:

14080

East Asian (EAS)

AF:

0.702

AC:

21291

AN:

30326

South Asian (SAS)

AF:

0.923

AC:

42752

AN:

46340

European-Finnish (FIN)

AF:

0.862

AC:

25593

AN:

29704

Middle Eastern (MID)

AF:

0.934

AC:

2111

AN:

2260

European-Non Finnish (NFE)

AF:

0.884

AC:

255330

AN:

288728

Other (OTH)

AF:

0.871

AC:

23342

AN:

26786

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

2556

5111

7667

10222

12778

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1458

2916

4374

5832

7290

<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:

0.884

AC:

134522

AN:

152148

Hom.:

59864

Cov.:

AF XY:

0.879

AC XY:

65366

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.953

AC:

39576

AN:

41532

American (AMR)

AF:

0.775

AC:

11851

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.866

AC:

3004

AN:

3468

East Asian (EAS)

AF:

0.701

AC:

3605

AN:

5144

South Asian (SAS)

AF:

0.911

AC:

4395

AN:

4822

European-Finnish (FIN)

AF:

0.850

AC:

9002

AN:

10590

Middle Eastern (MID)

AF:

0.939

AC:

276

AN:

294

European-Non Finnish (NFE)

AF:

0.885

AC:

60188

AN:

67980

Other (OTH)

AF:

0.886

AC:

1869

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

774

1547

2321

3094

3868

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

900

1800

2700

3600

4500

<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:

0.882

Hom.:

77597

Bravo

AF:

0.883

Asia WGS

AF:

0.809

AC:

2814

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.0080

(source)

DANN

Benign

0.14

PhyloP100

-5.5

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over