chr20-1318382-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_080489.5(SDCBP2):c.161T>C(p.Met54Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,454,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
SDCBP2
NM_080489.5 missense
NM_080489.5 missense
Scores
7
7
4
Clinical Significance
Conservation
PhyloP100: 6.96
Genes affected
SDCBP2 (HGNC:15756): (syndecan binding protein 2) The protein encoded by this gene contains two class II PDZ domains. PDZ domains facilitate protein-protein interactions by binding to the cytoplasmic C-terminus of transmembrane proteins, and PDZ-containing proteins mediate cell signaling and the organization of protein complexes. The encoded protein binds to phosphatidylinositol 4, 5-bisphosphate (PIP2) and plays a role in nuclear PIP2 organization and cell division. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. Read-through transcription also exists between this gene and the upstream FKBP1A (FK506 binding protein 1A, 12kDa) gene, as represented in GeneID:100528031. [provided by RefSeq, Sep 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.793
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SDCBP2 | NM_080489.5 | c.161T>C | p.Met54Thr | missense_variant | 4/9 | ENST00000360779.4 | |
FKBP1A-SDCBP2 | NR_037661.1 | n.439T>C | non_coding_transcript_exon_variant | 5/10 | |||
SDCBP2 | NM_001199784.2 | c.161T>C | p.Met54Thr | missense_variant | 4/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SDCBP2 | ENST00000360779.4 | c.161T>C | p.Met54Thr | missense_variant | 4/9 | 1 | NM_080489.5 | P1 | |
SDCBP2 | ENST00000339987.7 | c.161T>C | p.Met54Thr | missense_variant | 4/9 | 1 | P1 | ||
SDCBP2 | ENST00000381812.5 | c.161T>C | p.Met54Thr | missense_variant | 4/9 | 5 | P1 | ||
SDCBP2 | ENST00000615838.1 | n.235T>C | non_coding_transcript_exon_variant | 4/5 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000414 AC: 1AN: 241486Hom.: 0 AF XY: 0.00000761 AC XY: 1AN XY: 131474
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GnomAD4 exome AF: 6.87e-7 AC: 1AN: 1454754Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 723080
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GnomAD4 genome ? Cov.: 32
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32
Bravo
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 27, 2023 | The c.161T>C (p.M54T) alteration is located in exon 4 (coding exon 3) of the SDCBP2 gene. This alteration results from a T to C substitution at nucleotide position 161, causing the methionine (M) at amino acid position 54 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
T
MetaRNN
Pathogenic
D;D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;M;M
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
D;D;D
Vest4
MutPred
Loss of stability (P = 0.0348);Loss of stability (P = 0.0348);Loss of stability (P = 0.0348);
MVP
MPC
0.33
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at