NM_021938.4:c.661_664dupCGGC

Variant names:

• chr19-3281254-T-TCCGG
• rs1057518402
• NM_021938.4:c.661_664dupCGGC

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_021938.4(CELF5):​c.661_664dupCGGC​(p.Arg222ProfsTer181) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CELF5 NM_021938.4 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.509
• Publications: 0 publications found

Genes affected

CELF5 (HGNC:14058): (CUGBP Elav-like family member 5) This gene encodes a member of the the CELF/BRUNOL protein family, which contain two N-terminal RNA recognition motif (RRM) domains, one C-terminal RRM domain, and a divergent segment of 160-230 aa between the second and third RRM domains. Members of this protein family regulate pre-mRNA alternative splicing and may also be involved in mRNA editing and translation. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2012]

ACMG classification

Our verdict: Pathogenic. The variant received 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021938.4. 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
	CELF5	NM_021938.4	MANE Select	c.661_664dupCGGC	p.Arg222ProfsTer181	frameshift	Exon 6 of 13	NP_068757.2
	CELF5	NM_001172673.2		c.661_664dupCGGC	p.Arg222ProfsTer158	frameshift	Exon 6 of 12	NP_001166144.1	Q8N6W0-2
	CELF5	NR_033342.2		n.743_746dupCGGC		non_coding_transcript_exon	Exon 6 of 13

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELF5	ENST00000292672.7	TSL:1 MANE Select	c.661_664dupCGGC	p.Arg222ProfsTer181	frameshift	Exon 6 of 13	ENSP00000292672.1	Q8N6W0-1
	CELF5	ENST00000541430.6	TSL:1	c.661_664dupCGGC	p.Arg222ProfsTer158	frameshift	Exon 6 of 12	ENSP00000443498.1	Q8N6W0-2
	CELF5	ENST00000588350.1	TSL:1	n.244_247dupCGGC		non_coding_transcript_exon	Exon 4 of 11	ENSP00000468503.1	K7ES14

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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
PhyloP100		-0.51
Mutation Taster		=53/147	disease causing (fs/PTC)

Splicing

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

Other links and lift over

dbSNP: rs1057518402; hg19: chr19-3281252;