10-67891029-CAAAAAA-CAAAAAAA

Variant names:

• chr10-67891029-C-CA
• rs11327756
• NM_012238.5:c.790-359dupA

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_012238.5(SIRT1):​c.790-359dupA 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 0.0034 (1 hom., cov: 0)
• Consequence: SIRT1 NM_012238.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.155
• 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 344 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIRT1	NM_012238.5	c.790-359dupA		intron_variant	Intron 3 of 8	ENST00000212015.11	NP_036370.2
SIRT1	NM_001142498.2	c.-96-359dupA		intron_variant	Intron 2 of 7		NP_001135970.1
SIRT1	NM_001314049.2	c.-245-359dupA		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.790-373_790-372insA		intron_variant	Intron 3 of 8	1	NM_012238.5	ENSP00000212015.6
SIRT1	ENST00000432464.5	c.-96-373_-96-372insA		intron_variant	Intron 2 of 7	5		ENSP00000409208.1
SIRT1	ENST00000473922.1	n.334-373_334-372insA		intron_variant	Intron 2 of 3	4
SIRT1	ENST00000497639.5	n.579-373_579-372insA		intron_variant	Intron 3 of 3	5

Frequencies

GnomAD3 genomes AF: 0.00344 AC: 344 AN: 100050 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.00566

Gnomad AMI AF: 0.00159

Gnomad AMR AF: 0.00172

Gnomad ASJ AF: 0.00504

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00924

Gnomad FIN AF: 0.00108

Gnomad MID AF: 0.00442

Gnomad NFE AF: 0.00241

Gnomad OTH AF: 0.00599

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

GnomAD4 genome AF: 0.00344 AC: 344 AN: 100058 Hom.: 1 Cov.: 0 AF XY: 0.00395 AC XY: 188 AN XY: 47598

African (AFR) AF: 0.00565 AC: 159 AN: 28124

American (AMR) AF: 0.00172 AC: 17 AN: 9892

Ashkenazi Jewish (ASJ) AF: 0.00504 AC: 12 AN: 2382

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

South Asian (SAS) AF: 0.00928 AC: 32 AN: 3448

European-Finnish (FIN) AF: 0.00108 AC: 5 AN: 4632

Middle Eastern (MID) AF: 0.00485 AC: 1 AN: 206

European-Non Finnish (NFE) AF: 0.00241 AC: 109 AN: 45264

Other (OTH) AF: 0.00594 AC: 8 AN: 1346

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.15
Mutation Taster		=100/0	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: rs11327756; hg19: chr10-69650787;