chr8-143792019-CG-GC

Variant names:

• chr8-143792019-CG-GC
• NM_182706.5:c.4628_4629delCGinsGC
• SCRIB p.Ala1543Gly

Variant summary

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

The NM_182706.5(SCRIB):​c.4628_4629delCGinsGC​(p.Ala1543Gly) 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: SCRIB NM_182706.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.11
• Publications: 0 publications found

Genes affected

SCRIB (HGNC:30377): (scribble planar cell polarity protein) This gene encodes a protein that was identified as being similar to the Drosophila scribble protein. The mammalian protein is involved in tumor suppression pathways. As a scaffold protein involved in cell polarization processes, this protein binds to many other proteins. The encoded protein binds to papillomavirus E6 protein via its PDZ domain and the C-terminus of E6. Two alternatively spliced transcript variants that encode different protein isoforms have been found for this gene. [provided by RefSeq, Nov 2011]

SCRIB Gene-Disease associations (from GenCC):

• autism spectrum disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182706.5. 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
	SCRIB	NM_182706.5	MANE Select	c.4628_4629delCGinsGC	p.Ala1543Gly	missense	N/A	NP_874365.3
	SCRIB	NM_015356.5		c.4628_4629delCGinsGC	p.Ala1543Gly	missense	N/A	NP_056171.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCRIB	ENST00000356994.7	TSL:2 MANE Select	c.4628_4629delCGinsGC	p.Ala1543Gly	missense	N/A	ENSP00000349486.2	Q14160-3
	SCRIB	ENST00000320476.7	TSL:1	c.4628_4629delCGinsGC	p.Ala1543Gly	missense	N/A	ENSP00000322938.3	Q14160-1
	SCRIB	ENST00000377533.7	TSL:1	c.4385_4386delCGinsGC	p.Ala1462Gly	missense	N/A	ENSP00000366756.3	Q14160-2

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		4.1

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: chr8-144874189;