NM_080489.5:c.844C>T

Variant summary

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

The NM_080489.5(SDCBP2):​c.844C>T​(p.His282Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,422 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SDCBP2
NM_080489.5 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.28
Variant links:
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]
FKBP1A-SDCBP2 (HGNC:41997): (FKBP1A-SDCBP2 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring FK506 binding protein 1A, 12kDa and syndecan binding protein (syntenin) 2 genes on chromosome 20. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is unlikely to produce a protein product. [provided by RefSeq, Dec 2010]

Genome browser will be placed here

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=0.16175014).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SDCBP2NM_080489.5 linkc.844C>T p.His282Tyr missense_variant Exon 9 of 9 ENST00000360779.4 NP_536737.3 Q9H190-1
SDCBP2NM_001199784.2 linkc.844C>T p.His282Tyr missense_variant Exon 9 of 9 NP_001186713.1 Q9H190-1
SDCBP2NM_015685.6 linkc.589C>T p.His197Tyr missense_variant Exon 5 of 5 NP_056500.2 Q9H190-3
FKBP1A-SDCBP2NR_037661.1 linkn.1122C>T non_coding_transcript_exon_variant Exon 10 of 10

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SDCBP2ENST00000360779.4 linkc.844C>T p.His282Tyr missense_variant Exon 9 of 9 1 NM_080489.5 ENSP00000354013.3 Q9H190-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461422
Hom.:
0
Cov.:
34
AF XY:
0.00000138
AC XY:
1
AN XY:
727032
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jul 19, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.844C>T (p.H282Y) alteration is located in exon 9 (coding exon 8) of the SDCBP2 gene. This alteration results from a C to T substitution at nucleotide position 844, causing the histidine (H) at amino acid position 282 to be replaced by a tyrosine (Y). 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
0.10
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
23
DANN
Uncertain
0.98
DEOGEN2
Benign
0.052
T;.;T;T
Eigen
Benign
-0.013
Eigen_PC
Benign
0.069
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Benign
0.65
.;T;.;T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.16
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.1
M;.;M;M
PrimateAI
Benign
0.26
T
PROVEAN
Benign
-1.3
N;N;N;N
REVEL
Benign
0.039
Sift
Uncertain
0.0020
D;D;D;D
Sift4G
Uncertain
0.0040
D;D;D;D
Polyphen
0.36
B;.;B;B
Vest4
0.13
MutPred
0.49
Loss of disorder (P = 0.0406);.;Loss of disorder (P = 0.0406);Loss of disorder (P = 0.0406);
MVP
0.20
MPC
0.35
ClinPred
0.76
D
GERP RS
4.5
Varity_R
0.13
gMVP
0.37

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: chr20-1291120; API