Genetic Variant SBK1:p.Pro275Thr (chr16-28320469-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001024401.3(SBK1):c.823C>A(p.Pro275Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000211 in 1,422,412 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SBK1
NM_001024401.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.603

Publications

0 publications found

Variant links:

Genes affected

SBK1 (HGNC:17699): (SH3 domain binding kinase 1) Predicted to enable protein serine/threonine kinase activity. Predicted to be involved in peptidyl-serine phosphorylation and peptidyl-threonine phosphorylation. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

SBK1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25198013).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001024401.3. 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
	SBK1	NM_001024401.3	MANE Select	c.823C>A	p.Pro275Thr	missense	Exon 4 of 4	NP_001019572.1	Q52WX2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SBK1	ENST00000341901.5	TSL:1 MANE Select	c.823C>A	p.Pro275Thr	missense	Exon 4 of 4	ENSP00000343248.4	Q52WX2
	SBK1	ENST00000671413.3		c.1087C>A	p.Pro363Thr	missense	Exon 4 of 4	ENSP00000499661.3	A0A590UK17

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000485

AC:

AN:

206186

AF XY:

0.00000862

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000107

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000211

AC:

AN:

1422412

Hom.:

Cov.:

AF XY:

0.00000283

AC XY:

AN XY:

707806

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31948

American (AMR)

AF:

0.00

AC:

AN:

40864

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24960

East Asian (EAS)

AF:

0.00

AC:

AN:

38318

South Asian (SAS)

AF:

0.00

AC:

AN:

84682

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37922

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5610

European-Non Finnish (NFE)

AF:

0.00000273

AC:

AN:

1099412

Other (OTH)

AF:

0.00

AC:

AN:

58696

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.026

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.32

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.84

M_CAP

Pathogenic

0.80

MetaRNN

Benign

0.25

MetaSVM

Benign

-0.85

MutationAssessor

Benign

1.2

PhyloP100

0.60

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-0.59

REVEL

Benign

0.040

Sift

Benign

0.083

Sift4G

Benign

0.12

Polyphen

0.029

Vest4

0.093

MutPred

0.42

Gain of phosphorylation at P275 (P = 0.0438)

MVP

0.65

ClinPred

0.10

GERP RS

1.7

Varity_R

0.13

gMVP

0.81

Mutation Taster

=85/15

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over