8-58576021-AA-GG

Variant names:

• chr8-58576021-AA-GG
• NM_005625.4:c.362_363delAAinsGG
• SDCBP p.Gln121Arg

Variant summary

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

The NM_005625.4(SDCBP):​c.362_363delAAinsGG​(p.Gln121Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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)
• Consequence: SDCBP NM_005625.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.27
• Publications: 0 publications found

Genes affected

SDCBP (HGNC:10662): (syndecan binding protein) The protein encoded by this gene was initially identified as a molecule linking syndecan-mediated signaling to the cytoskeleton. The syntenin protein contains tandemly repeated PDZ domains that bind the cytoplasmic, C-terminal domains of a variety of transmembrane proteins. This protein may also affect cytoskeletal-membrane organization, cell adhesion, protein trafficking, and the activation of transcription factors. The protein is primarily localized to membrane-associated adherens junctions and focal adhesions but is also found at the endoplasmic reticulum and nucleus. Alternative splicing results in multiple transcript variants encoding different isoforms. Related pseudogenes have been identified on multiple chromosomes. [provided by RefSeq, Jan 2017]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005625.4. 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
	SDCBP	NM_005625.4	MANE Select	c.362_363delAAinsGG	p.Gln121Arg	missense	N/A	NP_005616.2	O00560-1
	SDCBP	NM_001348341.2		c.425_426delAAinsGG	p.Gln142Arg	missense	N/A	NP_001335270.1
	SDCBP	NM_001330537.2		c.422_423delAAinsGG	p.Gln141Arg	missense	N/A	NP_001317466.1	G5EA09

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDCBP	ENST00000260130.9	TSL:1 MANE Select	c.362_363delAAinsGG	p.Gln121Arg	missense	N/A	ENSP00000260130.4	O00560-1
	SDCBP	ENST00000447182.6	TSL:1	c.359_360delAAinsGG	p.Gln120Arg	missense	N/A	ENSP00000409288.2	O00560-2
	SDCBP	ENST00000523483.5	TSL:2	c.422_423delAAinsGG	p.Gln141Arg	missense	N/A	ENSP00000428184.1	G5EA09

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.3

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr8-59488580;