dbSNP rs1232322825: CELF6:p.Arg97Leu (chr15-72315900-C-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_052840.5(CELF6):c.290G>T(p.Arg97Leu) 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 pathogenic 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. R97Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CELF6
NM_052840.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.57

Publications

0 publications found

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:

ENSG00000260729 (HGNC:):

ENSG00000260729 links:

ENSG00000261460 (HGNC:58304):

ENSG00000261460 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.835

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELF6	NM_052840.5 link	c.290G>T	p.Arg97Leu	missense_variant	Exon 2 of 13	ENST00000287202.10	NP_443072.3
CELF6	NM_001172684.2 link	c.290G>T	p.Arg97Leu	missense_variant	Exon 2 of 12		NP_001166155.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CELF6	ENST00000287202.10 link	c.290G>T	p.Arg97Leu	missense_variant	Exon 2 of 13	1	NM_052840.5	ENSP00000287202.5	Q96J87-1
ENSG00000260729	ENST00000379915.4 link	n.*1042G>T		non_coding_transcript_exon_variant	Exon 7 of 16	2		ENSP00000478716.1	A0A087WUJ7
ENSG00000273025	ENST00000569547.1 link	n.290G>T		non_coding_transcript_exon_variant	Exon 2 of 15	2		ENSP00000454749.1
ENSG00000260729	ENST00000379915.4 link	n.*1042G>T		3_prime_UTR_variant	Exon 7 of 16	2		ENSP00000478716.1	A0A087WUJ7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1455796

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723476

African (AFR)

AF:

0.00

AC:

AN:

33386

American (AMR)

AF:

0.00

AC:

AN:

43930

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25962

East Asian (EAS)

AF:

0.00

AC:

AN:

39548

South Asian (SAS)

AF:

0.00

AC:

AN:

84794

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52776

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5704

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109532

Other (OTH)

AF:

0.00

AC:

AN:

60164

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.86

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.060

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.031

T;.

Eigen

Uncertain

0.65

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

.;D

M_CAP

Benign

0.043

MetaRNN

Pathogenic

0.83

D;D

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;L

PhyloP100

7.6

PrimateAI

Pathogenic

0.90

PROVEAN

Pathogenic

-5.4

D;D

REVEL

Uncertain

0.43

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.011

D;D

Polyphen

0.65

P;.

Vest4

0.88

MutPred

0.61

Gain of ubiquitination at K102 (P = 0.0693);Gain of ubiquitination at K102 (P = 0.0693);

MVP

0.46

MPC

1.9

ClinPred

1.0

GERP RS

6.0

Varity_R

0.63

gMVP

0.69

Mutation Taster

=11/89

disease causing

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over