10-67884727-G-A

Variant names:

• chr10-67884727-G-A
• rs995528945
• NM_012238.5:c.6G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_012238.5(SIRT1):​c.6G>A​(p.Ala2Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000371 in 1,076,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000037 (0 hom.)
• Consequence: SIRT1 NM_012238.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.31
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BP6: Variant 10-67884727-G-A is Benign according to our data. Variant chr10-67884727-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2045818.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=3.31 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIRT1	NM_012238.5	c.6G>A	p.Ala2Ala	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.6G>A	p.Ala2Ala	synonymous_variant	Exon 1 of 9	1	NM_012238.5	ENSP00000212015.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000371 AC: 4 AN: 1076870 Hom.: 0 Cov.: 31 AF XY: 0.00000197 AC XY: 1 AN XY: 508512

African (AFR) AF: 0.00 AC: 0 AN: 22784

American (AMR) AF: 0.00 AC: 0 AN: 8338

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14242

East Asian (EAS) AF: 0.00 AC: 0 AN: 26406

South Asian (SAS) AF: 0.00 AC: 0 AN: 19356

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21080

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2930

European-Non Finnish (NFE) AF: 0.00000109 AC: 1 AN: 918296

Other (OTH) AF: 0.0000691 AC: 3 AN: 43438

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 28, 2021

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	16
DANN	Benign	0.96
PhyloP100		3.3
PromoterAI		-0.65	Under-expression
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs995528945; hg19: chr10-69644485;