rs1029959272

Variant names:

• chr10-67884928-TGCG-T
• rs1029959272
• NM_012238.5:c.220_222delGCG

Your query was ambiguous. Multiple possible variants found:

• chr10-67884928-TGCG-T
• chr10-67884928-TGCG-TGCGGCG
• chr10-67884928-TGCG-TGCGGCGGCG

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_012238.5(SIRT1):​c.220_222delGCG​(p.Ala74del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000376 in 1,090,178 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000038 (0 hom.)
• Consequence: SIRT1 NM_012238.5 conservative_inframe_deletion
• 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 -1 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_012238.5

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIRT1	NM_012238.5	c.220_222delGCG	p.Ala74del	conservative_inframe_deletion	Exon 1 of 9	ENST00000212015.11	NP_036370.2
SIRT1	NM_001142498.2	c.-684_-682delGCG		upstream_gene_variant			NP_001135970.1
SIRT1	NM_001314049.2	c.-1075_-1073delGCG		upstream_gene_variant			NP_001300978.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIRT1	ENST00000212015.11	c.220_222delGCG	p.Ala74del	conservative_inframe_deletion	Exon 1 of 9	1	NM_012238.5	ENSP00000212015.6
SIRT1	ENST00000432464.5	c.-684_-682delGCG		upstream_gene_variant		5		ENSP00000409208.1
SIRT1	ENST00000497639.5	n.-252_-250delGCG		upstream_gene_variant		5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 3024 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000376 AC: 41 AN: 1090178 Hom.: 0 AF XY: 0.0000482 AC XY: 25 AN XY: 518470

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

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

American (AMR) AF: 0.00 AC: 0 AN: 8162

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

East Asian (EAS) AF: 0.0000379 AC: 1 AN: 26380

South Asian (SAS) AF: 0.000242 AC: 5 AN: 20680

European-Finnish (FIN) AF: 0.0000746 AC: 2 AN: 26810

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3220

European-Non Finnish (NFE) AF: 0.0000324 AC: 30 AN: 925076

Other (OTH) AF: 0.0000689 AC: 3 AN: 43510

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3
Mutation Taster		=83/17	polymorphism

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

Other links and lift over

dbSNP: rs1029959272; hg19: chr10-69644686;