Genetic Variant SIRT4:c.-1572C>G (chr12-120291724-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The XM_006719309.5(SIRT4):c.-1572C>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 151,914 control chromosomes in the GnomAD database, including 36,258 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 0.69 ( 36256 hom., cov: 31)

Exomes 𝑓: 0.83 ( 2 hom. )

Consequence

SIRT4
XM_006719309.5 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.253

Variant links:

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]

SIRT4 links:

RNU4-2 (HGNC:10193): (RNA, U4 small nuclear 2)

RNU4-2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.875 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIRT4	XM_006719309.5 link	c.-1572C>G		upstream_gene_variant			XP_006719372.1	Q9Y6E7
RNU4-2	NR_003137.3 link	n.*35G>C		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNU4-2	ENST00000365668.1 link	n.*39G>C		downstream_gene_variant		6

Frequencies

GnomAD3 genomes

AF:

0.688

AC:

104384

AN:

151790

Hom.:

36234

Cov.:

show subpopulations

Gnomad AFR

AF:

0.642

Gnomad AMI

AF:

0.834

Gnomad AMR

AF:

0.639

Gnomad ASJ

AF:

0.549

Gnomad EAS

AF:

0.896

Gnomad SAS

AF:

0.808

Gnomad FIN

AF:

0.736

Gnomad MID

AF:

0.655

Gnomad NFE

AF:

0.699

Gnomad OTH

AF:

0.698

GnomAD4 exome

AF:

0.833

AC:

AN:

Hom.:

Cov.:

AF XY:

1.00

AC XY:

AN XY:

show subpopulations

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

0.750

GnomAD4 genome

AF:

0.688

AC:

104456

AN:

151908

Hom.:

36256

Cov.:

AF XY:

0.690

AC XY:

51243

AN XY:

74264

show subpopulations

Gnomad4 AFR

AF:

0.642

Gnomad4 AMR

AF:

0.639

Gnomad4 ASJ

AF:

0.549

Gnomad4 EAS

AF:

0.896

Gnomad4 SAS

AF:

0.809

Gnomad4 FIN

AF:

0.736

Gnomad4 NFE

AF:

0.699

Gnomad4 OTH

AF:

0.703

Alfa

AF:

0.602

Hom.:

1705

Bravo

AF:

0.679

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.032

DANN

Benign

0.14

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over