Genetic Variant CELF3:p.Gln367_Gln373del (chr1-151706231-TTGCTGCTGCTGCTGTTGCTGC-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_007185.7(CELF3):c.1098_1118delGCAGCAACAGCAGCAGCAGCA(p.Gln367_Gln373del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000123 in 1,608,240 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

CELF3
NM_007185.7 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.15

Variant links:

Genes affected

CELF3 (HGNC:11967): (CUGBP Elav-like family member 3) Members of the CELF/BRUNOL protein family 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. Multiple alternatively spliced transcript variants encoding different isoforms have been identified in this gene. [provided by RefSeq, Feb 2010]

CELF3 links:

ENSG00000227045 (HGNC:):

ENSG00000227045 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELF3	NM_007185.7 link	c.1098_1118delGCAGCAACAGCAGCAGCAGCA	p.Gln367_Gln373del	disruptive_inframe_deletion	Exon 10 of 13	ENST00000290583.9	NP_009116.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CELF3	ENST00000290583.9 link	c.1098_1118delGCAGCAACAGCAGCAGCAGCA	p.Gln367_Gln373del	disruptive_inframe_deletion	Exon 10 of 13	1	NM_007185.7	ENSP00000290583.4		Q5SZQ8-1

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

151872

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000972

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000255

AC:

AN:

235634

Hom.:

AF XY:

0.00000782

AC XY:

AN XY:

127890

show subpopulations

Gnomad AFR exome

AF:

0.0000681

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000572

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000381

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000122

AC:

177

AN:

1456368

Hom.:

AF XY:

0.000122

AC XY:

AN XY:

724206

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000154

Gnomad4 OTH exome

AF:

0.0000831

GnomAD4 genome

AF:

0.000138

AC:

AN:

151872

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74200

show subpopulations

Gnomad4 AFR

AF:

0.0000972

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.000121

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Neuromuscular disease

Uncertain:1

Nov 22, 2024

Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: curation

The heterozygous p.Gln367_Gln373del variant in CELF3 was identified by our study, in the compound heterozygous state with another variant of uncertain significance, in 1 individual with neuromuscular disease. While this gene is still lacking sufficient evidence to establish a gene-disease relationship, we believe this is a possible novel gene candidate for neuromuscular disease. Given the limited information about this gene-disease relationship, the significance of the p.Gln367_Gln373del variant is uncertain. If you have any additional information about functional evidence or other individuals with this phenotype that also have variants in CELF3 we encourage you to reach out to us. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over