chr16-28320469-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 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. 13/20 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

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.603
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]

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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=0.25198013).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SBK1NM_001024401.3 linkc.823C>A p.Pro275Thr missense_variant Exon 4 of 4 ENST00000341901.5 NP_001019572.1 Q52WX2
SBK1XM_005255315.5 linkc.925C>A p.Pro309Thr missense_variant Exon 4 of 4 XP_005255372.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SBK1ENST00000341901.5 linkc.823C>A p.Pro275Thr missense_variant Exon 4 of 4 1 NM_001024401.3 ENSP00000343248.4 Q52WX2
SBK1ENST00000671413.3 linkc.1087C>A p.Pro363Thr missense_variant Exon 4 of 4 ENSP00000499661.3 A0A590UK17

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.00000485
AC:
1
AN:
206186
Hom.:
0
AF XY:
0.00000862
AC XY:
1
AN XY:
116022
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 SAS 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:
3
AN:
1422412
Hom.:
0
Cov.:
32
AF XY:
0.00000283
AC XY:
2
AN XY:
707806
show subpopulations
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:
0.00000273
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
May 23, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.823C>A (p.P275T) alteration is located in exon 4 (coding exon 3) of the SBK1 gene. This alteration results from a C to A substitution at nucleotide position 823, causing the proline (P) at amino acid position 275 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
21
DANN
Uncertain
0.98
DEOGEN2
Benign
0.026
T
Eigen
Benign
-0.41
Eigen_PC
Benign
-0.32
FATHMM_MKL
Benign
0.63
D
LIST_S2
Benign
0.84
T
M_CAP
Pathogenic
0.80
D
MetaRNN
Benign
0.25
T
MetaSVM
Benign
-0.85
T
MutationAssessor
Benign
1.2
L
PrimateAI
Uncertain
0.79
T
PROVEAN
Benign
-0.59
N
REVEL
Benign
0.040
Sift
Benign
0.083
T
Sift4G
Benign
0.12
T
Polyphen
0.029
B
Vest4
0.093
MutPred
0.42
Gain of phosphorylation at P275 (P = 0.0438);
MVP
0.65
ClinPred
0.10
T
GERP RS
1.7
Varity_R
0.13
gMVP
0.81

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

LitVar

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

Other links and lift over

dbSNP: rs1390511083; hg19: chr16-28331790; API