12-6872349-T-A

Variant summary

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

The NM_032641.4(SPSB2):​c.553A>T​(p.Thr185Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

SPSB2
NM_032641.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.76
Variant links:
Genes affected
SPSB2 (HGNC:29522): (splA/ryanodine receptor domain and SOCS box containing 2) This gene encodes a member of a subfamily of proteins containing a central SPRY (repeats in splA and RyR) domain and a C-terminal suppressor of cytokine signaling (SOCS) box. This protein plays a role in cell signaling. This gene is present in a gene-rich cluster on chromosome 12p13 in the vicinity of the CD4 antigen and triosephosphate isomerase genes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

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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=0.16421935).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SPSB2NM_032641.4 linkc.553A>T p.Thr185Ser missense_variant Exon 2 of 3 ENST00000524270.6 NP_116030.1 Q99619-1
SPSB2NM_001146316.2 linkc.553A>T p.Thr185Ser missense_variant Exon 2 of 3 NP_001139788.1 Q99619-1
SPSB2NM_001319670.2 linkc.553A>T p.Thr185Ser missense_variant Exon 1 of 2 NP_001306599.1 Q99619-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SPSB2ENST00000524270.6 linkc.553A>T p.Thr185Ser missense_variant Exon 2 of 3 1 NM_032641.4 ENSP00000428338.1 Q99619-1
SPSB2ENST00000523102.5 linkc.553A>T p.Thr185Ser missense_variant Exon 2 of 3 1 ENSP00000430872.1 Q99619-1
SPSB2ENST00000519357.1 linkc.553A>T p.Thr185Ser missense_variant Exon 2 of 2 2 ENSP00000431037.1 Q99619-2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Aug 21, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.553A>T (p.T185S) alteration is located in exon 2 (coding exon 1) of the SPSB2 gene. This alteration results from a A to T substitution at nucleotide position 553, causing the threonine (T) at amino acid position 185 to be replaced by a serine (S). 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
0.076
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
23
DANN
Benign
0.89
DEOGEN2
Benign
0.098
T;T;.
Eigen
Benign
-0.32
Eigen_PC
Benign
-0.24
FATHMM_MKL
Benign
0.61
D
LIST_S2
Benign
0.61
.;T;T
M_CAP
Benign
0.028
D
MetaRNN
Benign
0.16
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.38
N;N;N
PrimateAI
Benign
0.39
T
PROVEAN
Benign
0.32
N;N;N
REVEL
Benign
0.052
Sift
Uncertain
0.024
D;D;T
Sift4G
Benign
0.077
T;T;T
Polyphen
0.12
B;B;.
Vest4
0.47
MutPred
0.45
Gain of catalytic residue at Y186 (P = 0);Gain of catalytic residue at Y186 (P = 0);Gain of catalytic residue at Y186 (P = 0);
MVP
0.15
MPC
0.38
ClinPred
0.45
T
GERP RS
3.7
Varity_R
0.18
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-6981513; API