chr19-3290285-C-G

Variant summary

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

The NM_021938.4(CELF5):​c.1241C>G​(p.Thr414Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,638 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign 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. T414M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 30)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

CELF5
NM_021938.4 missense

Scores

16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.52
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]

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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=0.0799562).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CELF5NM_021938.4 linkc.1241C>G p.Thr414Arg missense_variant Exon 11 of 13 ENST00000292672.7 NP_068757.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CELF5ENST00000292672.7 linkc.1241C>G p.Thr414Arg missense_variant Exon 11 of 13 1 NM_021938.4 ENSP00000292672.1 Q8N6W0-1

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461638
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
727130
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.20
BayesDel_addAF
Benign
-0.070
T
BayesDel_noAF
Benign
-0.48
CADD
Uncertain
25
DANN
Benign
0.96
Eigen
Benign
-0.088
Eigen_PC
Benign
-0.044
FATHMM_MKL
Benign
0.68
D
LIST_S2
Benign
0.38
T
M_CAP
Benign
0.0072
T
MetaRNN
Benign
0.080
T
MetaSVM
Benign
-1.1
T
PROVEAN
Benign
1.4
N
REVEL
Benign
0.092
Sift
Benign
0.079
T
Sift4G
Benign
0.22
T
Polyphen
0.0
B
Vest4
0.19
MVP
0.47
ClinPred
0.55
D
GERP RS
0.79

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-3290283; API