rs4807546

Positions:

• chr19-4182063-T-C
• chr19-4182063-T-G

Variant summary

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

The NM_016539.4(SIRT6):​c.66+411A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 169,270 control chromosomes in the GnomAD database, including 1,723 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 0.12 (1564 hom., cov: 32)
  • Exomes 𝑓: 0.11 (159 hom.)
• Consequence: SIRT6 NM_016539.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.41

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIRT6	NM_016539.4	c.66+411A>G		intron_variant		ENST00000337491.7	NP_057623.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIRT6	ENST00000337491.7	c.66+411A>G		intron_variant		1	NM_016539.4	ENSP00000337332.1

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18721 AN: 151854 Hom.: 1564 Cov.: 32

Gnomad AFR AF: 0.0658

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.361

Gnomad SAS AF: 0.0935

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.118

GnomAD4 exome AF: 0.112 AC: 1941 AN: 17296 Hom.: 159 AF XY: 0.110 AC XY: 1026 AN XY: 9340

Gnomad4 AFR exome AF: 0.0635

Gnomad4 AMR exome AF: 0.205

Gnomad4 ASJ exome AF: 0.122

Gnomad4 EAS exome AF: 0.322

Gnomad4 SAS exome AF: 0.0673

Gnomad4 FIN exome AF: 0.110

Gnomad4 NFE exome AF: 0.100

Gnomad4 OTH exome AF: 0.119

GnomAD4 genome AF: 0.123 AC: 18734 AN: 151974 Hom.: 1564 Cov.: 32 AF XY: 0.128 AC XY: 9511 AN XY: 74266

Gnomad4 AFR AF: 0.0659

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.134

Gnomad4 EAS AF: 0.360

Gnomad4 SAS AF: 0.0938

Gnomad4 FIN AF: 0.149

Gnomad4 NFE AF: 0.116

Gnomad4 OTH AF: 0.119

Alfa AF: 0.120 Hom.: 2426

Bravo AF: 0.126

Asia WGS AF: 0.213 AC: 740 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	1.2
DANN	Benign	0.87

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: rs4807546; hg19: chr19-4182060;