12-120310110-G-T

Variant names:

• chr12-120310110-G-T
• rs2522129
• NM_012240.3:c.498-2346G>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.498-2346G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 151,814 control chromosomes in the GnomAD database, including 4,358 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 0.21 (4358 hom., cov: 30)
• Consequence: SIRT4 NM_012240.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.286
• Publications: 9 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012240.3. 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
	SIRT4	NM_012240.3	MANE Select	c.498-2346G>T		intron	N/A	NP_036372.1
	SIRT4	NM_001385733.2		c.498-2346G>T		intron	N/A	NP_001372662.1
	SIRT4	NM_001385734.1		c.225-2346G>T		intron	N/A	NP_001372663.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIRT4	ENST00000202967.4	TSL:1 MANE Select	c.498-2346G>T		intron	N/A	ENSP00000202967.4
	SIRT4	ENST00000850925.1		c.225-2346G>T		intron	N/A	ENSP00000521005.1
	SIRT4	ENST00000537892.1	TSL:5	n.180-2474G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32410 AN: 151696 Hom.: 4358 Cov.: 30

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.0692

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.0832

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.170

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.214 AC: 32433 AN: 151814 Hom.: 4358 Cov.: 30 AF XY: 0.209 AC XY: 15509 AN XY: 74194

African (AFR) AF: 0.388 AC: 16027 AN: 41350

American (AMR) AF: 0.151 AC: 2290 AN: 15200

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

East Asian (EAS) AF: 0.0828 AC: 428 AN: 5168

South Asian (SAS) AF: 0.125 AC: 598 AN: 4796

European-Finnish (FIN) AF: 0.158 AC: 1669 AN: 10548

Middle Eastern (MID) AF: 0.169 AC: 49 AN: 290

European-Non Finnish (NFE) AF: 0.155 AC: 10531 AN: 67982

Other (OTH) AF: 0.166 AC: 348 AN: 2102

Alfa AF: 0.167 Hom.: 1302

Bravo AF: 0.221

Asia WGS AF: 0.133 AC: 464 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.69
DANN	Benign	0.63
PhyloP100		-0.29
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: rs2522129; hg19: chr12-120747913;