Variant chr12-120312436-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

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. There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.71 ( 38534 hom., cov: 32)

Exomes 𝑓: 0.71 ( 364679 hom. )

Consequence

SIRT4
NM_012240.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0250

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 2 / 10). 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 linkuse as main transcript	c.498-20A>G		intron_variant		ENST00000202967.4

Ensembl

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

Frequencies

GnomAD3 genomes

AF:

0.709

AC:

107809

AN:

151956

Hom.:

38512

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.711

AC XY:

506944

AN XY:

712724

show subpopulations

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.:

AF XY:

0.706

AC XY:

52481

AN XY:

74330

show subpopulations

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

BranchPoint Hunter

2.0

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

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