11-47487212-T-C

Position:

• chr11-47487212-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001376376.1(CELF1):​c.289A>G​(p.Lys97Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CELF1 NM_001376376.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.86

Genes affected

CELF1 (HGNC:2549): (CUGBP Elav-like family member 1) 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. This gene may play a role in myotonic dystrophy type 1 (DM1) via interactions with the dystrophia myotonica-protein kinase (DMPK) gene. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30746418).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CELF1	NM_001376376.1	c.289A>G	p.Lys97Glu	missense_variant	5/15	ENST00000687097.1	NP_001363305.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CELF1	ENST00000687097.1	c.289A>G	p.Lys97Glu	missense_variant	5/15		NM_001376376.1	ENSP00000508525.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 20, 2024

The c.289A>G (p.K97E) alteration is located in exon 5 (coding exon 3) of the CELF1 gene. This alteration results from a A to G substitution at nucleotide position 289, causing the lysine (K) at amino acid position 97 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.16
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	.;.;T;.;.;.;.;T;.;.;T;T
Eigen	Benign	0.095
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;D;D;.;D;D;D;D;D;D;D;D
M_CAP	Benign	0.070	D
MetaRNN	Benign	0.31	T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.56	T
MutationAssessor	Benign	-1.5	N;N;N;N;N;.;.;.;.;.;.;.
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.46	N;N;N;N;N;N;N;D;D;D;D;D
REVEL	Uncertain	0.37
Sift	Benign	0.53	T;T;T;T;T;T;T;T;T;T;T;T
Sift4G	Benign	0.28	T;T;T;T;T;T;T;.;T;T;.;T
Polyphen		0.94	P;.;P;B;B;B;P;.;.;.;.;.
Vest4		0.70
MutPred		0.37		.;.;.;.;.;Loss of ubiquitination at K97 (P = 0.0155);Loss of ubiquitination at K97 (P = 0.0155);.;Loss of ubiquitination at K97 (P = 0.0155);.;.;Loss of ubiquitination at K97 (P = 0.0155);
MVP		0.87
MPC		1.7
ClinPred		0.73	D
GERP RS		5.9
Varity_R		0.65
gMVP		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-47508764;