chr19-38897076-G-A

Variant names:

• chr19-38897076-G-A
• rs4802998
• NM_012237.4:c.63+1303C>T

Variant summary

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

The NM_012237.4(SIRT2):​c.63+1303C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.711 in 152,152 control chromosomes in the GnomAD database, including 39,416 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 0.71 (39416 hom., cov: 32)
• Consequence: SIRT2 NM_012237.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.340
• Publications: 15 publications found

Genes affected

SIRT2 (HGNC:10886): (sirtuin 2) 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. Several transcript variants are resulted from alternative splicing of this gene. [provided by RefSeq, Jul 2010]

ENSG00000305081 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.945 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012237.4. 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
	SIRT2	NM_012237.4	MANE Select	c.63+1303C>T		intron	N/A	NP_036369.2
	SIRT2	NM_030593.3		c.-49+2430C>T		intron	N/A	NP_085096.1
	SIRT2	NM_001193286.2		c.-49+2430C>T		intron	N/A	NP_001180215.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIRT2	ENST00000249396.12	TSL:1 MANE Select	c.63+1303C>T		intron	N/A	ENSP00000249396.7
	SIRT2	ENST00000392081.6	TSL:1	c.-49+2430C>T		intron	N/A	ENSP00000375931.2
	SIRT2	ENST00000872149.1		c.63+1303C>T		intron	N/A	ENSP00000542208.1

Frequencies

GnomAD3 genomes AF: 0.711 AC: 108106 AN: 152034 Hom.: 39359 Cov.: 32

Gnomad AFR AF: 0.839

Gnomad AMI AF: 0.560

Gnomad AMR AF: 0.759

Gnomad ASJ AF: 0.691

Gnomad EAS AF: 0.967

Gnomad SAS AF: 0.744

Gnomad FIN AF: 0.693

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.607

Gnomad OTH AF: 0.698

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

GnomAD4 genome AF: 0.711 AC: 108219 AN: 152152 Hom.: 39416 Cov.: 32 AF XY: 0.719 AC XY: 53526 AN XY: 74394

African (AFR) AF: 0.839 AC: 34826 AN: 41494

American (AMR) AF: 0.759 AC: 11604 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.691 AC: 2395 AN: 3468

East Asian (EAS) AF: 0.967 AC: 5016 AN: 5188

South Asian (SAS) AF: 0.743 AC: 3586 AN: 4828

European-Finnish (FIN) AF: 0.693 AC: 7330 AN: 10580

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.607 AC: 41275 AN: 67996

Other (OTH) AF: 0.700 AC: 1479 AN: 2112

Alfa AF: 0.654 Hom.: 63248

Bravo AF: 0.723

Asia WGS AF: 0.859 AC: 2985 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	5.6
DANN	Benign	0.74
PhyloP100		0.34
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: rs4802998; hg19: chr19-39387716;