rs107251

chr19-4176088-T-C

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.47

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIRT6	NM_016539.4	c.438-151A>G		intron_variant		ENST00000337491.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIRT6	ENST00000337491.7	c.438-151A>G		intron_variant		1	NM_016539.4	P1

Frequencies

GnomAD3 genomes AF: 0.884 AC: 134417 AN: 152030 Hom.: 59820 Cov.: 31

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

Gnomad4 AFR exome AF: 0.955

Gnomad4 AMR exome AF: 0.745

Gnomad4 ASJ exome AF: 0.863

Gnomad4 EAS exome AF: 0.702

Gnomad4 SAS exome AF: 0.923

Gnomad4 FIN exome AF: 0.862

Gnomad4 NFE exome AF: 0.884

Gnomad4 OTH exome AF: 0.871

GnomAD4 genome AF: 0.884 AC: 134522 AN: 152148 Hom.: 59864 Cov.: 31 AF XY: 0.879 AC XY: 65366 AN XY: 74390

Gnomad4 AFR AF: 0.953

Gnomad4 AMR AF: 0.775

Gnomad4 ASJ AF: 0.866

Gnomad4 EAS AF: 0.701

Gnomad4 SAS AF: 0.911

Gnomad4 FIN AF: 0.850

Gnomad4 NFE AF: 0.885

Gnomad4 OTH AF: 0.886

Alfa AF: 0.880 Hom.: 59769

Bravo AF: 0.883

Asia WGS AF: 0.809 AC: 2814 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.0080
Dann	Benign	0.14

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: rs107251; hg19: chr19-4176085;