chr10-67891029-CAAA-C

Variant names:

• chr10-67891029-CAAA-C
• rs11327756
• NM_012238.5:c.790-361_790-359delAAA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_012238.5(SIRT1):​c.790-361_790-359delAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000010 (0 hom., cov: 0)
• Consequence: SIRT1 NM_012238.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.251
• Publications: 1 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]

SIRT1 Gene-Disease associations (from GenCC):

• autoimmune disease

  Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia
• monogenic diabetes

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012238.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIRT1	NM_012238.5	MANE Select	c.790-361_790-359delAAA		intron	N/A	NP_036370.2
	SIRT1	NM_001142498.2		c.-96-361_-96-359delAAA		intron	N/A	NP_001135970.1	E9PC49
	SIRT1	NM_001314049.2		c.-245-361_-245-359delAAA		intron	N/A	NP_001300978.1	B0QZ35

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIRT1	ENST00000212015.11	TSL:1 MANE Select	c.790-372_790-370delAAA		intron	N/A	ENSP00000212015.6	Q96EB6-1
	SIRT1	ENST00000923649.1		c.790-372_790-370delAAA		intron	N/A	ENSP00000593708.1
	SIRT1	ENST00000959939.1		c.790-372_790-370delAAA		intron	N/A	ENSP00000629998.1

Frequencies

GnomAD3 genomes AF: 0.00000996 AC: 1 AN: 100406 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

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: 0.0000220

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00000996 AC: 1 AN: 100414 Hom.: 0 Cov.: 0 AF XY: 0.0000209 AC XY: 1 AN XY: 47766

African (AFR) AF: 0.00 AC: 0 AN: 28182

American (AMR) AF: 0.00 AC: 0 AN: 9900

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2394

East Asian (EAS) AF: 0.00 AC: 0 AN: 4134

South Asian (SAS) AF: 0.00 AC: 0 AN: 3456

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4634

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 206

European-Non Finnish (NFE) AF: 0.0000220 AC: 1 AN: 45524

Other (OTH) AF: 0.00 AC: 0 AN: 1352

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.25

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs11327756; hg19: chr10-69650787;