Genetic Variant CELF3:p.Ala312Glu (chr1-151706722-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007185.7(CELF3):c.935C>A(p.Ala312Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000143 in 1,397,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A312V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CELF3
NM_007185.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.60

Publications

0 publications found

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 was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21554223).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007185.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CELF3	NM_007185.7	MANE Select	c.935C>A	p.Ala312Glu	missense	Exon 9 of 13	NP_009116.3
CELF3	NM_001291106.2		c.935C>A	p.Ala312Glu	missense	Exon 9 of 13	NP_001278035.1	Q5SZQ8-2
CELF3	NM_001291107.2		c.932C>A	p.Ala311Glu	missense	Exon 9 of 13	NP_001278036.1	Q5SZQ8-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CELF3	ENST00000290583.9	TSL:1 MANE Select	c.935C>A	p.Ala312Glu	missense	Exon 9 of 13	ENSP00000290583.4	Q5SZQ8-1
CELF3	ENST00000290585.8	TSL:1	c.785C>A	p.Ala262Glu	missense	Exon 8 of 12	ENSP00000290585.4	Q5SZQ8-4
CELF3	ENST00000420342.1	TSL:5	c.935C>A	p.Ala312Glu	missense	Exon 10 of 14	ENSP00000402503.1	H0Y623

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000143

AC:

AN:

1397798

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

689450

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31570

American (AMR)

AF:

0.00

AC:

AN:

35578

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25056

East Asian (EAS)

AF:

0.00

AC:

AN:

35728

South Asian (SAS)

AF:

0.00

AC:

AN:

79126

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48934

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5574

European-Non Finnish (NFE)

AF:

0.00000185

AC:

AN:

1078302

Other (OTH)

AF:

0.00

AC:

AN:

57930

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.0017

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.20

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.055

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.0073

MetaRNN

Benign

0.22

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

PhyloP100

4.6

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.9

REVEL

Benign

0.10

Sift

Uncertain

0.017

Sift4G

Benign

0.22

Polyphen

0.89

Vest4

0.52

MutPred

0.34

Gain of solvent accessibility (P = 0.0016)

MVP

0.28

MPC

0.38

ClinPred

0.44

GERP RS

4.4

Varity_R

0.20

gMVP

0.59

Mutation Taster

=80/20

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over