rs2261612

chr12-120312436-A-Gchr12-120312436-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012240.3(SIRT4):c.498-20A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.71 in 1,588,520 control chromosomes in the GnomAD database, including 403,213 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 (38534 hom., cov: 32)
  • Exomes 𝑓: 0.71 (364679 hom.)
• Consequence: SIRT4 NM_012240.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0250

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIRT4	NM_012240.3	c.498-20A>G		intron_variant		ENST00000202967.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIRT4	ENST00000202967.4	c.498-20A>G		intron_variant		1	NM_012240.3	P1
SIRT4	ENST00000537892.1	n.180-148A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.709 AC: 107809 AN: 151956 Hom.: 38512 Cov.: 32

Gnomad AFR AF: 0.724

Gnomad AMI AF: 0.796

Gnomad AMR AF: 0.734

Gnomad ASJ AF: 0.592

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.740

Gnomad FIN AF: 0.710

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.715

Gnomad OTH AF: 0.715

GnomAD3 exomes AF: 0.702 AC: 163810 AN: 233376 Hom.: 58267 AF XY: 0.704 AC XY: 89108 AN XY: 126510

Gnomad AFR exome AF: 0.727

Gnomad AMR exome AF: 0.747

Gnomad ASJ exome AF: 0.601

Gnomad EAS exome AF: 0.463

Gnomad SAS exome AF: 0.750

Gnomad FIN exome AF: 0.710

Gnomad NFE exome AF: 0.719

Gnomad OTH exome AF: 0.708

GnomAD4 exome AF: 0.711 AC: 1020692 AN: 1436446 Hom.: 364679 Cov.: 39 AF XY: 0.711 AC XY: 506944 AN XY: 712724

Gnomad4 AFR exome AF: 0.727

Gnomad4 AMR exome AF: 0.748

Gnomad4 ASJ exome AF: 0.606

Gnomad4 EAS exome AF: 0.466

Gnomad4 SAS exome AF: 0.744

Gnomad4 FIN exome AF: 0.714

Gnomad4 NFE exome AF: 0.718

Gnomad4 OTH exome AF: 0.703

GnomAD4 genome AF: 0.709 AC: 107890 AN: 152074 Hom.: 38534 Cov.: 32 AF XY: 0.706 AC XY: 52481 AN XY: 74330

Gnomad4 AFR AF: 0.724

Gnomad4 AMR AF: 0.734

Gnomad4 ASJ AF: 0.592

Gnomad4 EAS AF: 0.477

Gnomad4 SAS AF: 0.740

Gnomad4 FIN AF: 0.710

Gnomad4 NFE AF: 0.715

Gnomad4 OTH AF: 0.718

Alfa AF: 0.710 Hom.: 52895

Bravo AF: 0.712

Asia WGS AF: 0.683 AC: 2373 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.9
Dann	Benign	0.15

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2261612; hg19: chr12-120750239; COSMIC: COSV52541841; COSMIC: COSV52541841;