19-36017450-CCT-GCG

Variant names:

• chr19-36017450-CCT-GCG
• NM_015526.3:c.1452-2_1452delAGGinsCGC
• CLIP3 p.Arg484Ser

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PVS1_Moderate

The NM_015526.3(CLIP3):​c.1452-2_1452delAGGinsCGC​(p.Arg484Ser) variant causes a splice acceptor, missense, splice region, intron 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. Synonymous variant affecting the same amino acid position (i.e. R484R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CLIP3 NM_015526.3 splice_acceptor, missense, splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.81
• Publications: 0 publications found

Genes affected

CLIP3 (HGNC:24314): (CAP-Gly domain containing linker protein 3) This gene encodes a member of the cytoplasmic linker protein 170 family. Members of this protein family contain a cytoskeleton-associated protein glycine-rich domain and mediate the interaction of microtubules with cellular organelles. The encoded protein plays a role in T cell apoptosis by facilitating the association of tubulin and the lipid raft ganglioside GD3. The encoded protein also functions as a scaffold protein mediating membrane localization of phosphorylated protein kinase B. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Dec 2010]

ENSG00000267698 (HGNC:):

ACMG classification

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

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.039537713 fraction of the gene. Cryptic splice site detected, with MaxEntScore 3.1, offset of 33, new splice context is: actgattcccccggggacAGcgt. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015526.3. 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
	CLIP3	NM_015526.3	MANE Select	c.1452-2_1452delAGGinsCGC	p.Arg484Ser	splice_acceptor missense splice_region intron	N/A	NP_056341.1	Q96DZ5
	CLIP3	NM_001199570.2		c.1452-2_1452delAGGinsCGC	p.Arg484Ser	splice_acceptor missense splice_region intron	N/A	NP_001186499.1	Q96DZ5
	LOC101927572	NR_170987.1		n.234+490_234+492delCCTinsGCG		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLIP3	ENST00000360535.9	TSL:1 MANE Select	c.1452-2_1452delAGGinsCGC	p.Arg484Ser	splice_acceptor missense splice_region intron	N/A	ENSP00000353732.3	Q96DZ5
	ENSG00000267698	ENST00000586962.1	TSL:1	n.228+490_228+492delCCTinsGCG		intron	N/A
	CLIP3	ENST00000593074.5	TSL:2	c.1452-2_1452delAGGinsCGC	p.Arg484Ser	splice_acceptor missense splice_region intron	N/A	ENSP00000466832.1	Q96DZ5

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		3.8

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: chr19-36508352;