NM_012238.5:c.943-5190T>C

Variant names:

• chr10-67901600-T-C
• rs33955981
• NM_012238.5:c.943-5190T>C

Variant summary

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

The NM_012238.5(SIRT1):​c.943-5190T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 152,052 control chromosomes in the GnomAD database, including 30,652 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 0.63 (30652 hom., cov: 32)
• Consequence: SIRT1 NM_012238.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.117
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIRT1	NM_012238.5	c.943-5190T>C		intron_variant	Intron 4 of 8	ENST00000212015.11	NP_036370.2
SIRT1	NM_001142498.2	c.58-5190T>C		intron_variant	Intron 3 of 7		NP_001135970.1
SIRT1	NM_001314049.2	c.-92-4563T>C		intron_variant	Intron 4 of 9		NP_001300978.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIRT1	ENST00000212015.11	c.943-5190T>C		intron_variant	Intron 4 of 8	1	NM_012238.5	ENSP00000212015.6
SIRT1	ENST00000432464.5	c.58-5190T>C		intron_variant	Intron 3 of 7	5		ENSP00000409208.1
SIRT1	ENST00000406900.5	c.-92-4563T>C		intron_variant	Intron 1 of 6	2		ENSP00000384508.1
SIRT1	ENST00000473922.1	n.487-5190T>C		intron_variant	Intron 3 of 3	4

Frequencies

GnomAD3 genomes AF: 0.626 AC: 95142 AN: 151932 Hom.: 30631 Cov.: 32

Gnomad AFR AF: 0.649

Gnomad AMI AF: 0.528

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.681

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.591

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.678

Gnomad OTH AF: 0.623

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

GnomAD4 genome AF: 0.626 AC: 95203 AN: 152052 Hom.: 30652 Cov.: 32 AF XY: 0.617 AC XY: 45863 AN XY: 74346

African (AFR) AF: 0.648 AC: 26889 AN: 41472

American (AMR) AF: 0.570 AC: 8694 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.681 AC: 2362 AN: 3470

East Asian (EAS) AF: 0.151 AC: 782 AN: 5166

South Asian (SAS) AF: 0.454 AC: 2189 AN: 4822

European-Finnish (FIN) AF: 0.591 AC: 6245 AN: 10568

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.678 AC: 46060 AN: 67982

Other (OTH) AF: 0.626 AC: 1319 AN: 2108

Alfa AF: 0.656 Hom.: 4842

Bravo AF: 0.622

Asia WGS AF: 0.389 AC: 1355 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.0
DANN	Benign	0.70
PhyloP100		-0.12
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: rs33955981; hg19: chr10-69661358;