12-120293066-G-C

Variant names:

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

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>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000457 in 124,702 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 0.00046 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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=-0.66).

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>C		intron	N/A	NP_001372662.1	Q9Y6E7
	SIRT4	NM_001385735.2		c.-2+124G>C		intron	N/A	NP_001372664.1
	RNU4-1	NR_003925.2		n.*27C>G		downstream_gene	N/A

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes AF: 0.000458 AC: 57 AN: 124582 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000747

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000328

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000156

Gnomad OTH AF: 0.000595

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 18 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 12

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 10

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.000457 AC: 57 AN: 124702 Hom.: 0 Cov.: 33 AF XY: 0.000417 AC XY: 25 AN XY: 59990

African (AFR) AF: 0.00106 AC: 37 AN: 34890

American (AMR) AF: 0.000746 AC: 9 AN: 12066

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 3344

South Asian (SAS) AF: 0.000328 AC: 1 AN: 3046

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 258

European-Non Finnish (NFE) AF: 0.000156 AC: 9 AN: 57658

Other (OTH) AF: 0.000588 AC: 1 AN: 1700

Alfa AF: 0.00 Hom.: 392

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.0010
DANN	Benign	0.43
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;