NM_012238.5:c.943-1588C>A

Variant names:

• chr10-67905202-C-A
• rs10997868
• NM_012238.5:c.943-1588C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012238.5(SIRT1):​c.943-1588C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 152,072 control chromosomes in the GnomAD database, including 20,722 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.47 (20722 hom., cov: 33)
• Consequence: SIRT1 NM_012238.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0610
• Publications: 11 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIRT1	NM_012238.5	MANE Select	c.943-1588C>A		intron	N/A	NP_036370.2
	SIRT1	NM_001142498.2		c.58-1588C>A		intron	N/A	NP_001135970.1
	SIRT1	NM_001314049.2		c.-92-961C>A		intron	N/A	NP_001300978.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIRT1	ENST00000212015.11	TSL:1 MANE Select	c.943-1588C>A		intron	N/A	ENSP00000212015.6
	SIRT1	ENST00000432464.5	TSL:5	c.58-1588C>A		intron	N/A	ENSP00000409208.1
	SIRT1	ENST00000406900.5	TSL:2	c.-92-961C>A		intron	N/A	ENSP00000384508.1

Frequencies

GnomAD3 genomes AF: 0.469 AC: 71278 AN: 151954 Hom.: 20726 Cov.: 33

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.670

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.506

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

GnomAD4 genome AF: 0.469 AC: 71267 AN: 152072 Hom.: 20722 Cov.: 33 AF XY: 0.465 AC XY: 34570 AN XY: 74344

African (AFR) AF: 0.138 AC: 5739 AN: 41498

American (AMR) AF: 0.504 AC: 7698 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.670 AC: 2321 AN: 3462

East Asian (EAS) AF: 0.149 AC: 771 AN: 5172

South Asian (SAS) AF: 0.441 AC: 2125 AN: 4816

European-Finnish (FIN) AF: 0.585 AC: 6166 AN: 10540

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.658 AC: 44748 AN: 67978

Other (OTH) AF: 0.510 AC: 1079 AN: 2116

Alfa AF: 0.585 Hom.: 67516

Bravo AF: 0.444

Asia WGS AF: 0.345 AC: 1202 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	8.3
DANN	Benign	0.86
PhyloP100		0.061
Mutation Taster		=100/0	polymorphism (auto)

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: rs10997868; hg19: chr10-69664959;