NM_001370096.2:c.743C>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001370096.2(SBK2):​c.743C>T​(p.Ala248Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000201 in 1,490,088 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A248G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

SBK2
NM_001370096.2 missense

Scores

6
11
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.61
Variant links:
Genes affected
SBK2 (HGNC:34416): (SH3 domain binding kinase family member 2) Predicted to enable MAP kinase kinase activity. Predicted to be involved in MAPK cascade and protein phosphorylation. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SBK2NM_001370096.2 linkc.743C>T p.Ala248Val missense_variant Exon 4 of 4 ENST00000413299.6 NP_001357025.1
SBK2XM_011527227.3 linkc.*302C>T 3_prime_UTR_variant Exon 4 of 4 XP_011525529.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SBK2ENST00000413299.6 linkc.743C>T p.Ala248Val missense_variant Exon 4 of 4 5 NM_001370096.2 ENSP00000389015.2 P0C263
SBK2ENST00000344158.4 linkc.743C>T p.Ala248Val missense_variant Exon 3 of 3 2 ENSP00000345044.3 P0C263

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152174
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
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
AF:
0.00000149
AC:
2
AN:
1337914
Hom.:
0
Cov.:
34
AF XY:
0.00000152
AC XY:
1
AN XY:
657290
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:
0.00000189
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152174
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74344
show subpopulations
Gnomad4 AFR
AF:
0.0000241
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
Bravo
AF:
0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.71
BayesDel_addAF
Pathogenic
0.19
D
BayesDel_noAF
Uncertain
0.030
CADD
Pathogenic
31
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.16
T;T
Eigen
Uncertain
0.68
Eigen_PC
Uncertain
0.54
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.90
D;.
M_CAP
Uncertain
0.12
D
MetaRNN
Uncertain
0.62
D;D
MetaSVM
Uncertain
-0.065
T
MutationAssessor
Pathogenic
4.3
H;H
PrimateAI
Pathogenic
0.89
D
PROVEAN
Uncertain
-3.5
D;D
REVEL
Uncertain
0.44
Sift
Uncertain
0.0020
D;D
Sift4G
Uncertain
0.010
D;D
Polyphen
1.0
D;D
Vest4
0.56
MutPred
0.70
Gain of helix (P = 0.2059);Gain of helix (P = 0.2059);
MVP
0.76
MPC
2.1
ClinPred
1.0
D
GERP RS
3.0
Varity_R
0.51
gMVP
0.79

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.

Other links and lift over

dbSNP: rs546747792; hg19: chr19-56041404; API