Genetic Variant CELF3:p.Ala312Val (chr1-151706722-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007185.7(CELF3):c.935C>T(p.Ala312Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000361 in 1,550,044 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

CELF3
NM_007185.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.60

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08870691).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELF3	NM_007185.7 link	c.935C>T	p.Ala312Val	missense_variant	Exon 9 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.935C>T	p.Ala312Val	missense_variant	Exon 9 of 13	1	NM_007185.7	ENSP00000290583.4		Q5SZQ8-1

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000532

AC:

AN:

150382

Hom.:

AF XY:

0.0000250

AC XY:

AN XY:

79902

show subpopulations

Gnomad AFR exome

AF:

0.000527

Gnomad AMR exome

AF:

0.0000816

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000883

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000250

AC:

AN:

1397798

Hom.:

Cov.:

AF XY:

0.0000160

AC XY:

AN XY:

689450

show subpopulations

Gnomad4 AFR exome

AF:

0.000570

Gnomad4 AMR exome

AF:

0.0000562

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000253

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000927

Gnomad4 OTH exome

AF:

0.0000518

GnomAD4 genome

AF:

0.000138

AC:

AN:

152246

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.000362

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000833

Hom.:

Bravo

AF:

0.000219

ESP6500AA

AF:

0.000266

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000206

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 21, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.935C>T (p.A312V) alteration is located in exon 9 (coding exon 9) of the CELF3 gene. This alteration results from a C to T substitution at nucleotide position 935, causing the alanine (A) at amino acid position 312 to be replaced by a valine (V). 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

Benign

0.078

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.48

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

.;T

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.052

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.95

D;D

M_CAP

Benign

0.0053

MetaRNN

Benign

0.089

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.29

.;N

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-0.64

N;N

REVEL

Benign

0.051

Sift

Benign

0.30

T;T

Sift4G

Benign

0.23

T;T

Polyphen

0.0080

.;B

Vest4

0.41

MVP

0.30

MPC

0.32

ClinPred

0.026

GERP RS

4.4

Varity_R

0.082

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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