NM_012240.3:c.498-3882C>T

Variant names:

• chr12-120308574-C-T
• rs7137625
• NM_012240.3:c.498-3882C>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.498-3882C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0803 in 152,082 control chromosomes in the GnomAD database, including 1,416 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 0.080 (1416 hom., cov: 31)
• Consequence: SIRT4 NM_012240.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.441
• Publications: 3 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.257 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIRT4	NM_012240.3	MANE Select	c.498-3882C>T		intron	N/A	NP_036372.1	Q9Y6E7
	SIRT4	NM_001385733.2		c.498-3882C>T		intron	N/A	NP_001372662.1	Q9Y6E7
	SIRT4	NM_001385734.1		c.225-3882C>T		intron	N/A	NP_001372663.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIRT4	ENST00000202967.4	TSL:1 MANE Select	c.498-3882C>T		intron	N/A	ENSP00000202967.4	Q9Y6E7
	SIRT4	ENST00000851536.1		c.516-3882C>T		intron	N/A	ENSP00000521595.1
	SIRT4	ENST00000851533.1		c.498-3882C>T		intron	N/A	ENSP00000521592.1

Frequencies

GnomAD3 genomes AF: 0.0802 AC: 12186 AN: 151964 Hom.: 1416 Cov.: 31

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0276

Gnomad ASJ AF: 0.00548

Gnomad EAS AF: 0.0590

Gnomad SAS AF: 0.0319

Gnomad FIN AF: 0.0178

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00254

Gnomad OTH AF: 0.0527

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

GnomAD4 genome AF: 0.0803 AC: 12208 AN: 152082 Hom.: 1416 Cov.: 31 AF XY: 0.0781 AC XY: 5809 AN XY: 74376

African (AFR) AF: 0.261 AC: 10826 AN: 41430

American (AMR) AF: 0.0276 AC: 421 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00548 AC: 19 AN: 3470

East Asian (EAS) AF: 0.0588 AC: 304 AN: 5174

South Asian (SAS) AF: 0.0324 AC: 156 AN: 4822

European-Finnish (FIN) AF: 0.0178 AC: 189 AN: 10606

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.00254 AC: 173 AN: 68008

Other (OTH) AF: 0.0521 AC: 110 AN: 2110

Alfa AF: 0.0313 Hom.: 684

Bravo AF: 0.0895

Asia WGS AF: 0.0670 AC: 235 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.38
PhyloP100		-0.44
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: rs7137625; hg19: chr12-120746377;