NM_080489.5:c.274G>A

Variant names:

• chr20-1313450-C-T
• rs753344660
• NM_080489.5:c.274G>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_080489.5(SDCBP2):​c.274G>A​(p.Gly92Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000345 in 1,448,296 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: SDCBP2 NM_080489.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.49
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.921

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.274G>A	p.Gly92Arg	missense	Exon 5 of 9	NP_536737.3
	SDCBP2	NM_001199784.2		c.274G>A	p.Gly92Arg	missense	Exon 5 of 9	NP_001186713.1	Q9H190-1
	SDCBP2	NM_015685.6		c.19G>A	p.Gly7Arg	missense	Exon 1 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.274G>A	p.Gly92Arg	missense	Exon 5 of 9	ENSP00000354013.3	Q9H190-1
	SDCBP2	ENST00000339987.7	TSL:1	c.274G>A	p.Gly92Arg	missense	Exon 5 of 9	ENSP00000342935.3	Q9H190-1
	SDCBP2	ENST00000381808.7	TSL:1	c.19G>A	p.Gly7Arg	missense	Exon 1 of 5	ENSP00000371229.3	Q9H190-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000446 AC: 1 AN: 224350 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000992

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000345 AC: 5 AN: 1448296 Hom.: 0 Cov.: 31 AF XY: 0.00000417 AC XY: 3 AN XY: 719726

African (AFR) AF: 0.0000301 AC: 1 AN: 33260

American (AMR) AF: 0.00 AC: 0 AN: 43792

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25864

East Asian (EAS) AF: 0.00 AC: 0 AN: 39198

South Asian (SAS) AF: 0.0000237 AC: 2 AN: 84318

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48796

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5606

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1107600

Other (OTH) AF: 0.00 AC: 0 AN: 59862

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Benign	0.64	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.061	D
MetaRNN	Pathogenic	0.92	D
MetaSVM	Benign	-0.42	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		5.5
PrimateAI	Uncertain	0.64	T
PROVEAN	Pathogenic	-6.8	D
REVEL	Uncertain	0.43
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0070	D
Polyphen		1.0	D
Vest4		0.88
MutPred		0.72		Gain of MoRF binding (P = 0.0073)
MVP		0.66
MPC		0.70
ClinPred		0.98	D
GERP RS		4.2
PromoterAI		-0.036	Neutral
Varity_R		0.64
gMVP		0.85
Mutation Taster		=48/52	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

dbSNP: rs753344660; hg19: chr20-1294094;