20-1318400-G-A

Variant names:

• chr20-1318400-G-A
• rs2088809405
• NM_080489.5:c.143C>T

Variant summary

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

The NM_080489.5(SDCBP2):​c.143C>T​(p.Ala48Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,449,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.572

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]

ENSG00000274322 (HGNC:):

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.143C>T	p.Ala48Val	missense_variant	Exon 4 of 9	ENST00000360779.4	NP_536737.3
SDCBP2	NM_001199784.2	c.143C>T	p.Ala48Val	missense_variant	Exon 4 of 9		NP_001186713.1
FKBP1A-SDCBP2	NR_037661.1	n.421C>T		non_coding_transcript_exon_variant	Exon 5 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDCBP2	ENST00000360779.4	c.143C>T	p.Ala48Val	missense_variant	Exon 4 of 9	1	NM_080489.5	ENSP00000354013.3
ENSG00000274322	ENST00000617804.1	n.*97C>T		non_coding_transcript_exon_variant	Exon 6 of 6	4		ENSP00000479180.1
ENSG00000274322	ENST00000617804.1	n.*97C>T		3_prime_UTR_variant	Exon 6 of 6	4		ENSP00000479180.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1449830 Hom.: 0 Cov.: 30 AF XY: 0.00000139 AC XY: 1 AN XY: 720138

Gnomad4 AFR exome AF: 0.0000304

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 11, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.143C>T (p.A48V) alteration is located in exon 4 (coding exon 3) of the SDCBP2 gene. This alteration results from a C to T substitution at nucleotide position 143, causing the alanine (A) at amino acid position 48 to be replaced by a valine (V). 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	0.12
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.035	T;T;T
Eigen	Benign	-0.086
Eigen_PC	Benign	-0.090
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.69	.;.;T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.6	M;M;M
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.3	N;N;N
REVEL	Benign	0.054
Sift	Benign	0.33	T;T;T
Sift4G	Benign	0.33	T;T;T
Polyphen		0.26	B;B;B
Vest4		0.33
MutPred		0.28		Loss of disorder (P = 0.0907);Loss of disorder (P = 0.0907);Loss of disorder (P = 0.0907);
MVP		0.39
MPC		0.29
ClinPred		0.83	D
GERP RS		3.9
Varity_R		0.073
gMVP		0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.22		Position offset: 18

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2088809405; hg19: chr20-1299044;