rs2522138

Variant names:

• chr12-120304341-A-G
• rs2522138
• NM_012240.3:c.497+283A>G

Your query was ambiguous. Multiple possible variants found:

• chr12-120304341-A-G
• chr12-120304341-A-T

Variant summary

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

The NM_012240.3(SIRT4):​c.497+283A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 152,018 control chromosomes in the GnomAD database, including 6,209 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 0.24 (6209 hom., cov: 32)
• Consequence: SIRT4 NM_012240.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22
• Publications: 8 publications found

Genes affected

SIRT4 (HGNC:14932): (sirtuin 4) 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 IV of the sirtuin family. [provided by RefSeq, Jul 2008]

ENSG00000298788 (HGNC:):

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 (AFR) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIRT4	NM_012240.3	c.497+283A>G		intron_variant	Intron 2 of 3	ENST00000202967.4	NP_036372.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIRT4	ENST00000202967.4	c.497+283A>G		intron_variant	Intron 2 of 3	1	NM_012240.3	ENSP00000202967.4
SIRT4	ENST00000850925.1	c.224+556A>G		intron_variant	Intron 2 of 3			ENSP00000521005.1
SIRT4	ENST00000537892.1	n.179+283A>G		intron_variant	Intron 1 of 2	5
ENSG00000298788	ENST00000758007.1	n.202-1725T>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36731 AN: 151900 Hom.: 6199 Cov.: 32

Gnomad AFR AF: 0.486

Gnomad AMI AF: 0.0670

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.0834

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.185

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

GnomAD4 genome AF: 0.242 AC: 36785 AN: 152018 Hom.: 6209 Cov.: 32 AF XY: 0.237 AC XY: 17621 AN XY: 74330

African (AFR) AF: 0.486 AC: 20134 AN: 41422

American (AMR) AF: 0.160 AC: 2448 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 430 AN: 3468

East Asian (EAS) AF: 0.0830 AC: 429 AN: 5170

South Asian (SAS) AF: 0.125 AC: 605 AN: 4822

European-Finnish (FIN) AF: 0.159 AC: 1678 AN: 10580

Middle Eastern (MID) AF: 0.175 AC: 51 AN: 292

European-Non Finnish (NFE) AF: 0.155 AC: 10564 AN: 67986

Other (OTH) AF: 0.183 AC: 385 AN: 2108

Alfa AF: 0.167 Hom.: 3535

Bravo AF: 0.254

Asia WGS AF: 0.141 AC: 493 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	4.8
DANN	Benign	0.68
PhyloP100		1.2
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: rs2522138; hg19: chr12-120742144;