Variant 18-45063547-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015559.3(SETBP1):c.4640C>T(p.Thr1547Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000077 in 129,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000077 ( 0 hom., cov: 24)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SETBP1
NM_015559.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.34

Variant links:

Genes affected

SETBP1 (HGNC:15573): (SET binding protein 1) This gene encodes a protein which contains a several motifs including a ski homology region and a SET-binding region in addition to three nuclear localization signals. The encoded protein has been shown to bind the SET nuclear oncogene which is involved in DNA replication. Mutations in this gene are associated with Schinzel-Giedion midface retraction syndrome. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

SETBP1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1516222).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SETBP1	NM_015559.3 linkuse as main transcript	c.4640C>T	p.Thr1547Ile	missense_variant	6/6	ENST00000649279.2	NP_056374.2	Q9Y6X0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SETBP1	ENST00000649279.2 linkuse as main transcript	c.4640C>T	p.Thr1547Ile	missense_variant	6/6		NM_015559.3	ENSP00000497406.1		Q9Y6X0-1

Frequencies

GnomAD3 genomes

AF:

0.00000770

AC:

AN:

129806

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000291

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1239052

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

610906

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000770

AC:

AN:

129806

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

62358

show subpopulations

Gnomad4 AFR

AF:

0.0000291

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

T;T

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.47

LIST_S2

Benign

0.51

.;T

M_CAP

Uncertain

0.25

MetaRNN

Benign

0.15

T;T

MetaSVM

Benign

-0.65

MutationAssessor

Benign

1.1

L;L

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.50

.;N

REVEL

Benign

0.039

Sift

Benign

0.20

.;T

Sift4G

Uncertain

0.044

.;D

Polyphen

0.13

B;B

Vest4

0.077

MutPred

0.20

Loss of phosphorylation at T1547 (P = 0.0031);Loss of phosphorylation at T1547 (P = 0.0031);

MVP

0.26

MPC

1.4

ClinPred

0.56

GERP RS

4.8

Varity_R

0.13

gMVP

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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