20-1312671-T-A

Variant names:

• chr20-1312671-T-A
• NM_080489.5:c.476A>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_080489.5(SDCBP2):​c.476A>T​(p.Asp159Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SDCBP2 NM_080489.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.26
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080489.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDCBP2	NM_080489.5	MANE Select	c.476A>T	p.Asp159Val	missense	Exon 6 of 9	NP_536737.3
	SDCBP2	NM_001199784.2		c.476A>T	p.Asp159Val	missense	Exon 6 of 9	NP_001186713.1	Q9H190-1
	SDCBP2	NM_015685.6		c.221A>T	p.Asp74Val	missense	Exon 2 of 5	NP_056500.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDCBP2	ENST00000360779.4	TSL:1 MANE Select	c.476A>T	p.Asp159Val	missense	Exon 6 of 9	ENSP00000354013.3	Q9H190-1
	SDCBP2	ENST00000339987.7	TSL:1	c.476A>T	p.Asp159Val	missense	Exon 6 of 9	ENSP00000342935.3	Q9H190-1
	SDCBP2	ENST00000381808.7	TSL:1	c.221A>T	p.Asp74Val	missense	Exon 2 of 5	ENSP00000371229.3	Q9H190-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.037	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	23
DANN	Benign	0.84
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.084
Eigen_PC	Benign	0.016
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.59	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		6.3
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.20
Sift	Benign	0.40	T
Sift4G	Benign	0.35	T
Polyphen		0.0060	B
Vest4		0.61
MutPred		0.63		Gain of MoRF binding (P = 0.0202)
MVP		0.51
MPC		0.78
ClinPred		0.63	D
GERP RS		4.5
Varity_R		0.39
gMVP		0.43
Mutation Taster		=58/42	polymorphism

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

Other links and lift over

hg19: chr20-1293315;