20-1312732-T-G

Variant names:

• chr20-1312732-T-G
• NM_080489.5:c.415A>C

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.67

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]

ACMG classification

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
SDCBP2	NM_080489.5	c.415A>C	p.Thr139Pro	missense_variant	Exon 6 of 9	ENST00000360779.4	NP_536737.3
SDCBP2	NM_001199784.2	c.415A>C	p.Thr139Pro	missense_variant	Exon 6 of 9		NP_001186713.1
SDCBP2	NM_015685.6	c.160A>C	p.Thr54Pro	missense_variant	Exon 2 of 5		NP_056500.2
FKBP1A-SDCBP2	NR_037661.1	n.693A>C		non_coding_transcript_exon_variant	Exon 7 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDCBP2	ENST00000360779.4	c.415A>C	p.Thr139Pro	missense_variant	Exon 6 of 9	1	NM_080489.5	ENSP00000354013.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461388 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 726996

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.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 03, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	22
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	D
LIST_S2	Uncertain	0.91	.;D;.;T
M_CAP	Uncertain	0.16	D
MetaRNN	Uncertain	0.57	D;D;D;D
MetaSVM	Uncertain	-0.23	T
MutationAssessor	Uncertain	2.7	M;.;M;M
PrimateAI	Benign	0.35	T
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	D
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.

Other links and lift over

hg19: chr20-1293376;