10-67884928-T-TGCGGCG

Variant names:

• chr10-67884928-T-TGCGGCG
• rs1029959272
• NM_012238.5:c.217_222dupGCGGCG

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP3 BS2

The NM_012238.5(SIRT1):​c.217_222dupGCGGCG​(p.Ala73_Ala74dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000567 in 1,235,292 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000046 (0 hom.)
• Consequence: SIRT1 NM_012238.5 conservative_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27
• Publications: 0 publications found

Genes affected

SIRT1 (HGNC:14929): (sirtuin 1) 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 I of the sirtuin family. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_012238.5
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIRT1	NM_012238.5	c.217_222dupGCGGCG	p.Ala73_Ala74dup	conservative_inframe_insertion	Exon 1 of 9	ENST00000212015.11	NP_036370.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIRT1	ENST00000212015.11	c.217_222dupGCGGCG	p.Ala73_Ala74dup	conservative_inframe_insertion	Exon 1 of 9	1	NM_012238.5	ENSP00000212015.6

Frequencies

GnomAD3 genomes AF: 0.0000138 AC: 2 AN: 144732 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000259

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000152

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000458 AC: 5 AN: 1090560 Hom.: 0 Cov.: 32 AF XY: 0.00000578 AC XY: 3 AN XY: 518684

African (AFR) AF: 0.00 AC: 0 AN: 22294

American (AMR) AF: 0.00 AC: 0 AN: 8166

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14046

East Asian (EAS) AF: 0.00 AC: 0 AN: 26404

South Asian (SAS) AF: 0.00 AC: 0 AN: 20690

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26838

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3222

European-Non Finnish (NFE) AF: 0.00000540 AC: 5 AN: 925368

Other (OTH) AF: 0.00 AC: 0 AN: 43532

GnomAD4 genome AF: 0.0000138 AC: 2 AN: 144732 Hom.: 0 Cov.: 33 AF XY: 0.0000142 AC XY: 1 AN XY: 70570

African (AFR) AF: 0.0000259 AC: 1 AN: 38542

American (AMR) AF: 0.00 AC: 0 AN: 14714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3396

East Asian (EAS) AF: 0.00 AC: 0 AN: 4778

South Asian (SAS) AF: 0.00 AC: 0 AN: 4504

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9788

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 270

European-Non Finnish (NFE) AF: 0.0000152 AC: 1 AN: 65886

Other (OTH) AF: 0.00 AC: 0 AN: 1988

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3
Mutation Taster		=82/18	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1029959272; hg19: chr10-69644686;