12-120293066-G-T

Variant names:

• chr12-120293066-G-T
• rs3847968
• XM_006719309.5:c.-230G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001385733.2(SIRT4):​c.-2+124G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000963 in 124,582 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000096 (0 hom., cov: 33)
• Consequence: SIRT4 NM_001385733.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 1 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:):

RNU4-1 (HGNC:10192): (RNA, U4 small nuclear 1)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001385733.2. 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_001385733.2		c.-2+124G>T		intron	N/A	NP_001372662.1	Q9Y6E7
	SIRT4	NM_001385735.2		c.-2+124G>T		intron	N/A	NP_001372664.1
	RNU4-1	NR_003925.2		n.*27C>A		downstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIRT4	ENST00000851533.1		c.-2+124G>T		intron	N/A	ENSP00000521592.1
	SIRT4	ENST00000851534.1		c.-2+822G>T		intron	N/A	ENSP00000521593.1
	SIRT4	ENST00000850925.1		c.-2+124G>T		intron	N/A	ENSP00000521005.1	A0ABJ7H8K5

Frequencies

GnomAD3 genomes AF: 0.0000963 AC: 12 AN: 124582 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000316

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000173

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.0000963 AC: 12 AN: 124582 Hom.: 0 Cov.: 33 AF XY: 0.0000835 AC XY: 5 AN XY: 59868

African (AFR) AF: 0.000316 AC: 11 AN: 34782

American (AMR) AF: 0.00 AC: 0 AN: 12044

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3134

East Asian (EAS) AF: 0.00 AC: 0 AN: 3348

South Asian (SAS) AF: 0.00 AC: 0 AN: 3048

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7862

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 276

European-Non Finnish (NFE) AF: 0.0000173 AC: 1 AN: 57662

Other (OTH) AF: 0.00 AC: 0 AN: 1682

Alfa AF: 0.00 Hom.: 392

Bravo AF: 0.0000793

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.0010
DANN	Benign	0.45
PhyloP100		-1.2

Splicing

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

Other links and lift over

dbSNP: rs3847968; hg19: chr12-120730869;