rs202116523

Variant names:

• chr10-67884769-G-A
• rs202116523
• NM_012238.5:c.48G>A

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_012238.5(SIRT1):​c.48G>A​(p.Ser16Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00354 in 1,227,948 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0032 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0036 (10 hom.)
• Consequence: SIRT1 NM_012238.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.693
• 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: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 10-67884769-G-A is Benign according to our data. Variant chr10-67884769-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1622951.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.693 with no splicing effect.
• BS2: High AC in GnomAd4 at 477 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIRT1	NM_012238.5	c.48G>A	p.Ser16Ser	synonymous_variant	Exon 1 of 9	ENST00000212015.11	NP_036370.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIRT1	ENST00000212015.11	c.48G>A	p.Ser16Ser	synonymous_variant	Exon 1 of 9	1	NM_012238.5	ENSP00000212015.6

Frequencies

GnomAD3 genomes AF: 0.00315 AC: 477 AN: 151286 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.000677

Gnomad AMI AF: 0.100

Gnomad AMR AF: 0.000591

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00454

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00442

Gnomad OTH AF: 0.00145

GnomAD2 exomes AF: 0.00 AC: 0 AN: 24 AF XY: 0.00

Gnomad NFE exome AF: 0.00

GnomAD4 exome AF: 0.00359 AC: 3865 AN: 1076560 Hom.: 10 Cov.: 31 AF XY: 0.00362 AC XY: 1838 AN XY: 508308

African (AFR) AF: 0.000307 AC: 7 AN: 22786

American (AMR) AF: 0.000723 AC: 6 AN: 8302

Ashkenazi Jewish (ASJ) AF: 0.000140 AC: 2 AN: 14236

East Asian (EAS) AF: 0.00 AC: 0 AN: 26404

South Asian (SAS) AF: 0.00 AC: 0 AN: 19428

European-Finnish (FIN) AF: 0.00437 AC: 92 AN: 21066

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2904

European-Non Finnish (NFE) AF: 0.00401 AC: 3684 AN: 918030

Other (OTH) AF: 0.00170 AC: 74 AN: 43404

GnomAD4 genome AF: 0.00315 AC: 477 AN: 151388 Hom.: 3 Cov.: 33 AF XY: 0.00341 AC XY: 252 AN XY: 73898

African (AFR) AF: 0.000675 AC: 28 AN: 41500

American (AMR) AF: 0.000590 AC: 9 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3440

East Asian (EAS) AF: 0.00 AC: 0 AN: 5114

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00454 AC: 48 AN: 10564

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.00442 AC: 298 AN: 67408

Other (OTH) AF: 0.00143 AC: 3 AN: 2096

Alfa AF: 0.00340 Hom.: 0

Bravo AF: 0.00302

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Mar 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SIRT1: BP4, BP7 -

Jan 28, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	11
DANN	Benign	0.94
PhyloP100		0.69
PromoterAI		-0.0022	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
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: rs202116523; hg19: chr10-69644527;