Variant 20-1312732-T-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_080489.5(SDCBP2):c.415A>C(p.Thr139Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,388 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SDCBP2
NM_080489.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.67

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]

SDCBP2 links:

FKBP1A-SDCBP2 (HGNC:):

FKBP1A-SDCBP2 links:

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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/exons	MANE
SDCBP2	NM_080489.5 linkuse as main transcript	c.415A>C	p.Thr139Pro	missense_variant	6/9	ENST00000360779.4
FKBP1A-SDCBP2	NR_037661.1 linkuse as main transcript	n.693A>C		non_coding_transcript_exon_variant	7/10
SDCBP2	NM_001199784.2 linkuse as main transcript	c.415A>C	p.Thr139Pro	missense_variant	6/9
SDCBP2	NM_015685.6 linkuse as main transcript	c.160A>C	p.Thr54Pro	missense_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SDCBP2	ENST00000360779.4 linkuse as main transcript	c.415A>C	p.Thr139Pro	missense_variant	6/9	1	NM_080489.5	P1	Q9H190-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461388

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726996

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jan 03, 2024

The c.415A>C (p.T139P) alteration is located in exon 6 (coding exon 5) of the SDCBP2 gene. This alteration results from a A to C substitution at nucleotide position 415, causing the threonine (T) at amino acid position 139 to be replaced by a proline (P). 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

Pathogenic

0.77

BayesDel_addAF

Uncertain

0.042

BayesDel_noAF

Benign

-0.18

Cadd

Benign

Dann

Benign

0.97

DEOGEN2

Benign

0.15

T;.;T;T

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.18

FATHMM_MKL

Uncertain

0.88

M_CAP

Uncertain

0.16

MetaRNN

Uncertain

0.57

D;D;D;D

MetaSVM

Uncertain

-0.23

MutationAssessor

Uncertain

2.7

M;.;M;M

MutationTaster

Benign

0.67

N;N;N;N

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-2.8

D;D;D;D

REVEL

Uncertain

0.38

Sift

Uncertain

0.0010

D;D;D;D

Sift4G

Uncertain

0.0030

D;D;D;D

Polyphen

0.25

B;.;B;B

Vest4

0.37

MutPred

0.73

Loss of phosphorylation at T139 (P = 0.0442);.;Loss of phosphorylation at T139 (P = 0.0442);Loss of phosphorylation at T139 (P = 0.0442);

MVP

0.74

MPC

0.59

ClinPred

0.97

GERP RS

3.4

Varity_R

0.81

gMVP

0.66

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over