19-3224786-T-C

Position:

• chr19-3224786-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021938.4(CELF5):​c.47T>C​(p.Leu16Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 30)
• Consequence: CELF5 NM_021938.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.14

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.060519516).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CELF5	NM_021938.4	c.47T>C	p.Leu16Pro	missense_variant	1/13	ENST00000292672.7	NP_068757.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CELF5	ENST00000292672.7	c.47T>C	p.Leu16Pro	missense_variant	1/13	1	NM_021938.4	ENSP00000292672	P1
CELF5	ENST00000541430.6	c.47T>C	p.Leu16Pro	missense_variant	1/12	1		ENSP00000443498

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 11, 2021

The c.47T>C (p.L16P) alteration is located in exon 1 (coding exon 1) of the CELF5 gene. This alteration results from a T to C substitution at nucleotide position 47, causing the leucine (L) at amino acid position 16 to be replaced by a proline (P). 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	0.061
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	20
DANN	Benign	0.41
DEOGEN2	Benign	0.035	T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.30	T;T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.061	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.34	N;N
MutationTaster	Benign	0.99	D;D
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	0.58	N;N
REVEL	Benign	0.020
Sift	Benign	0.12	T;T
Sift4G	Benign	0.22	T;T
Polyphen		0.0	B;B
Vest4		0.19
MutPred		0.25		Gain of glycosylation at L16 (P = 0.0323);Gain of glycosylation at L16 (P = 0.0323);
MVP		0.11
MPC		2.0
ClinPred		0.12	T
GERP RS		1.4
Varity_R		0.28
gMVP		0.49

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: chr19-3224784;