dbSNP rs6490288: ENSG00000310566:n.470+950G>T (chr12-120291724-C-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

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

The ENST00000850922.1(ENSG00000310566):n.470+950G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00415 in 152,008 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 0.0042 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ENSG00000310566
ENST00000850922.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.253

Publications

3 publications found

Variant links:

Genes affected

ENSG00000310566 (HGNC:):

ENSG00000310566 links:

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 Gene-Disease associations (from GenCC):

neurodevelopmental disorder with hypotonia, brain anomalies, distinctive facies, and absent language
Inheritance: AD Classification: STRONG Submitted by: G2P
syndromic complex neurodevelopmental disorder
Inheritance: AD Classification: STRONG Submitted by: Broad Center for Mendelian Genomics

RNU4-2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
ENSG00000310566	ENST00000850922.1 link	n.470+950G>T	intron_variant	Intron 2 of 5
ENSG00000310566	ENST00000850923.1 link	n.358+1156G>T	intron_variant	Intron 1 of 2
ENSG00000310566	ENST00000850924.1 link	n.358+1156G>T	intron_variant	Intron 1 of 2
RNU4-2	ENST00000365668.2 link	n.*35G>T	downstream_gene_variant		6

Frequencies

GnomAD3 genomes

AF:

0.00414

AC:

629

AN:

151890

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00243

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00576

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00449

Gnomad OTH

AF:

0.00144

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.00415

AC:

631

AN:

152008

Hom.:

Cov.:

AF XY:

0.00390

AC XY:

290

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.00510

AC:

211

AN:

41378

American (AMR)

AF:

0.00242

AC:

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.00288

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5180

South Asian (SAS)

AF:

0.000621

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00576

AC:

AN:

10584

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00449

AC:

305

AN:

67992

Other (OTH)

AF:

0.00142

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

110

146

183

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00266

Hom.:

1705

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.035

(source)

DANN

Benign

0.26

PhyloP100

-0.25

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over