rs7298516

Variant names:

• chr12-120292433-G-T
• rs7298516
• NM_001385733.2:c.-511G>T

Variant summary

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

The NM_001385733.2(SIRT4):​c.-511G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.743 in 151,858 control chromosomes in the GnomAD database, including 42,327 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 0.74 (42327 hom., cov: 30)
• Consequence: SIRT4 NM_001385733.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.926
• Publications: 4 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]

ENSG00000310566 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.954 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIRT4	NM_001385733.2	c.-511G>T		5_prime_UTR_variant	Exon 1 of 4		NP_001372662.1
SIRT4	NM_001385735.2	c.-511G>T		5_prime_UTR_variant	Exon 1 of 4		NP_001372664.1
SIRT4	XM_006719309.5	c.-863G>T		5_prime_UTR_variant	Exon 1 of 4		XP_006719372.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIRT4	ENST00000850925.1	c.-511G>T		5_prime_UTR_variant	Exon 1 of 4			ENSP00000521005.1
ENSG00000310566	ENST00000850922.1	n.470+241C>A		intron_variant	Intron 2 of 5
ENSG00000310566	ENST00000850923.1	n.358+447C>A		intron_variant	Intron 1 of 2
ENSG00000310566	ENST00000850924.1	n.358+447C>A		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.743 AC: 112714 AN: 151740 Hom.: 42288 Cov.: 30

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.883

Gnomad AMR AF: 0.782

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.976

Gnomad SAS AF: 0.868

Gnomad FIN AF: 0.806

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.752

Gnomad OTH AF: 0.753

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

GnomAD4 genome AF: 0.743 AC: 112801 AN: 151858 Hom.: 42327 Cov.: 30 AF XY: 0.748 AC XY: 55513 AN XY: 74214

African (AFR) AF: 0.664 AC: 27455 AN: 41354

American (AMR) AF: 0.782 AC: 11923 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.575 AC: 1992 AN: 3462

East Asian (EAS) AF: 0.977 AC: 5044 AN: 5164

South Asian (SAS) AF: 0.869 AC: 4185 AN: 4816

European-Finnish (FIN) AF: 0.806 AC: 8495 AN: 10542

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.752 AC: 51112 AN: 67968

Other (OTH) AF: 0.756 AC: 1591 AN: 2104

Alfa AF: 0.755 Hom.: 67546

Bravo AF: 0.736

Asia WGS AF: 0.900 AC: 3124 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.3
DANN	Benign	0.55
PhyloP100		-0.93

Splicing

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

Other links and lift over

dbSNP: rs7298516; hg19: chr12-120730236;