10-67891029-CAAAAAA-CAA

Variant names:

• chr10-67891029-CAAAA-C
• rs11327756
• NM_012238.5:c.790-362_790-359delAAAA

Variant summary

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

The NM_012238.5(SIRT1):​c.790-362_790-359delAAAA 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: 1.18
• 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]

ACMG classification

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIRT1	NM_012238.5	c.790-362_790-359delAAAA		intron_variant	Intron 3 of 8	ENST00000212015.11	NP_036370.2
SIRT1	NM_001142498.2	c.-96-362_-96-359delAAAA		intron_variant	Intron 2 of 7		NP_001135970.1
SIRT1	NM_001314049.2	c.-245-362_-245-359delAAAA		intron_variant	Intron 3 of 9		NP_001300978.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIRT1	ENST00000212015.11	c.790-372_790-369delAAAA		intron_variant	Intron 3 of 8	1	NM_012238.5	ENSP00000212015.6
SIRT1	ENST00000432464.5	c.-96-372_-96-369delAAAA		intron_variant	Intron 2 of 7	5		ENSP00000409208.1
SIRT1	ENST00000473922.1	n.334-372_334-369delAAAA		intron_variant	Intron 2 of 3	4
SIRT1	ENST00000497639.5	n.579-372_579-369delAAAA		intron_variant	Intron 3 of 3	5

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: 100406 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 47744

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

African (AFR) AF: 0.00 AC: 0 AN: 28144

American (AMR) AF: 0.00 AC: 0 AN: 9888

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 4146

South Asian (SAS) AF: 0.00 AC: 0 AN: 3470

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 226

European-Non Finnish (NFE) AF: 0.0000220 AC: 1 AN: 45530

Other (OTH) AF: 0.00 AC: 0 AN: 1342

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2

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: rs11327756; hg19: chr10-69650787;