Genetic Variant CELF5:p.Pro31Ser (chr19-3224830-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_021938.4(CELF5):c.91C>T(p.Pro31Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000154 in 1,429,718 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

CELF5
NM_021938.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.34

Publications

0 publications found

Variant links:

Genes affected

CELF5 (HGNC:14058): (CUGBP Elav-like family member 5) This gene encodes a member of the the CELF/BRUNOL protein family, which 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. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2012]

CELF5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.048660517).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021938.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELF5	NM_021938.4	MANE Select	c.91C>T	p.Pro31Ser	missense	Exon 1 of 13	NP_068757.2
	CELF5	NM_001172673.2		c.91C>T	p.Pro31Ser	missense	Exon 1 of 12	NP_001166144.1	Q8N6W0-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CELF5	ENST00000292672.7	TSL:1 MANE Select	c.91C>T	p.Pro31Ser	missense	Exon 1 of 13	ENSP00000292672.1	Q8N6W0-1
CELF5	ENST00000541430.6	TSL:1	c.91C>T	p.Pro31Ser	missense	Exon 1 of 12	ENSP00000443498.1	Q8N6W0-2
CELF5	ENST00000872552.1		c.91C>T	p.Pro31Ser	missense	Exon 1 of 13	ENSP00000542611.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000154

AC:

AN:

194270

AF XY:

0.0000188

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000700

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000120

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000154

AC:

AN:

1429718

Hom.:

Cov.:

AF XY:

0.00000988

AC XY:

AN XY:

708816

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32322

American (AMR)

AF:

0.0000503

AC:

AN:

39748

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25360

East Asian (EAS)

AF:

0.00

AC:

AN:

37560

South Asian (SAS)

AF:

0.00

AC:

AN:

82364

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50062

Middle Eastern (MID)

AF:

0.000356

AC:

AN:

5620

European-Non Finnish (NFE)

AF:

0.0000146

AC:

AN:

1097572

Other (OTH)

AF:

0.0000338

AC:

AN:

59110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

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:

0.00000378

ExAC

AF:

0.0000168

AC:

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

0.064

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.023

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.52

M_CAP

Pathogenic

0.47

MetaRNN

Benign

0.049

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.26

PhyloP100

1.3

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

0.18

REVEL

Benign

0.034

Sift

Benign

0.29

Sift4G

Benign

0.39

Polyphen

0.0080

Vest4

0.059

MutPred

0.25

Gain of phosphorylation at P31 (P = 0.0051)

MVP

0.14

MPC

1.4

ClinPred

0.033

GERP RS

1.2

PromoterAI

-0.024

Neutral

(source)

Varity_R

0.036

gMVP

0.31

Mutation Taster

=73/27

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