Variant 15-72289646-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000287202.10(CELF6):c.728G>T(p.Cys243Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000666 in 1,350,728 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000067 ( 0 hom. )

Consequence

CELF6
ENST00000287202.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.95

Variant links:

Genes affected

CELF6 (HGNC:14059): (CUGBP Elav-like family member 6) 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]

CELF6 links:

(HGNC:):

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=0.14203778).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CELF6	NM_052840.5 linkuse as main transcript	c.728G>T	p.Cys243Phe	missense_variant	6/13	ENST00000287202.10	NP_443072.3
CELF6	NM_001172684.2 linkuse as main transcript	c.728G>T	p.Cys243Phe	missense_variant	6/12		NP_001166155.1
CELF6	NM_001172685.2 linkuse as main transcript	c.383G>T	p.Cys128Phe	missense_variant	5/11		NP_001166156.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CELF6	ENST00000287202.10 linkuse as main transcript	c.728G>T	p.Cys243Phe	missense_variant	6/13	1	NM_052840.5	ENSP00000287202	P1	Q96J87-1
	ENST00000570175.1 linkuse as main transcript	n.165+10615C>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000203

AC:

AN:

98556

Hom.:

AF XY:

0.0000363

AC XY:

AN XY:

55124

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000139

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000329

GnomAD4 exome

AF:

0.00000666

AC:

AN:

1350728

Hom.:

Cov.:

AF XY:

0.00000751

AC XY:

AN XY:

666064

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000119

Gnomad4 SAS exome

AF:

0.0000132

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000713

GnomAD4 genome

Cov.:

Asia WGS

AF:

0.000289

AC:

AN:

3472

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2023

The c.728G>T (p.C243F) alteration is located in exon 6 (coding exon 6) of the CELF6 gene. This alteration results from a G to T substitution at nucleotide position 728, causing the cysteine (C) at amino acid position 243 to be replaced by a phenylalanine (F). 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

0.11

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0017

T;.;.;.

Eigen

Benign

-0.11

Eigen_PC

Benign

0.027

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.94

.;D;D;D

M_CAP

Benign

0.059

MetaRNN

Benign

0.14

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;.;.;L

MutationTaster

Benign

0.82

D;D;D;D;D

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

1.7

N;N;N;N

REVEL

Benign

0.074

Sift

Benign

0.21

T;T;T;T

Sift4G

Benign

0.55

T;T;T;T

Polyphen

0.48

P;.;B;.

Vest4

0.50

MutPred

0.47

Loss of helix (P = 0.1706);.;.;Loss of helix (P = 0.1706);

MVP

0.26

MPC

1.8

ClinPred

0.10

GERP RS

3.3

Varity_R

0.11

gMVP

0.92

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

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