Genetic Variant CELF3:p.Ala335Thr (chr1-151706347-C-T) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_007185.7(CELF3):c.1003G>A(p.Ala335Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000572 in 1,397,768 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: not found (cov: 33)

Exomes 𝑓: 0.0000057 ( 0 hom. )

Consequence

CELF3
NM_007185.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.00

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.38019982).

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.1003G>A	p.Ala335Thr	missense	Exon 10 of 13	NP_009116.3
CELF3	NM_001291106.2		c.1000G>A	p.Ala334Thr	missense	Exon 10 of 13	NP_001278035.1	Q5SZQ8-2
CELF3	NM_001291107.2		c.1000G>A	p.Ala334Thr	missense	Exon 10 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.1003G>A	p.Ala335Thr	missense	Exon 10 of 13	ENSP00000290583.4	Q5SZQ8-1
CELF3	ENST00000290585.8	TSL:1	c.853G>A	p.Ala285Thr	missense	Exon 9 of 12	ENSP00000290585.4	Q5SZQ8-4
CELF3	ENST00000420342.1	TSL:5	c.1003G>A	p.Ala335Thr	missense	Exon 11 of 14	ENSP00000402503.1	H0Y623

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000455

AC:

AN:

153706

AF XY:

0.0000495

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000283

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000572

AC:

AN:

1397768

Hom.:

Cov.:

AF XY:

0.00000580

AC XY:

AN XY:

689338

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31562

American (AMR)

AF:

0.000224

AC:

AN:

35688

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25080

East Asian (EAS)

AF:

0.00

AC:

AN:

35734

South Asian (SAS)

AF:

0.00

AC:

AN:

79150

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49236

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4848

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1078544

Other (OTH)

AF:

0.00

AC:

AN:

57926

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

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.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.46

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.017

MetaRNN

Benign

0.38

MetaSVM

Benign

-1.2

MutationAssessor

Benign

2.0

PhyloP100

4.0

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-2.2

REVEL

Benign

0.11

Sift

Benign

0.054

Sift4G

Benign

0.30

Polyphen

1.0

Vest4

0.65

MutPred

0.24

Gain of glycosylation at A335 (P = 0.0199)

MVP

0.27

MPC

0.98

ClinPred

0.22

GERP RS

4.8

Varity_R

0.20

gMVP

0.59

Mutation Taster

=66/34

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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