rs865957358

Variant names:

• chr19-3293439-C-G
• rs865957358
• NM_021938.4:c.1451C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-3293439-C-G
• chr19-3293439-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_021938.4(CELF5):​c.1451C>G​(p.Pro484Arg) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CELF5 NM_021938.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.74
• Publications: 0 publications found

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

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, 0.758

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.1451C>G	p.Pro484Arg	missense	Exon 12 of 13	NP_068757.2
	CELF5	NM_001172673.2		c.*105C>G		3_prime_UTR	Exon 12 of 12	NP_001166144.1	Q8N6W0-2
	CELF5	NR_033342.2		n.1492C>G		non_coding_transcript_exon	Exon 12 of 13

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELF5	ENST00000292672.7	TSL:1 MANE Select	c.1451C>G	p.Pro484Arg	missense	Exon 12 of 13	ENSP00000292672.1	Q8N6W0-1
	CELF5	ENST00000541430.6	TSL:1	c.*105C>G		3_prime_UTR	Exon 12 of 12	ENSP00000443498.1	Q8N6W0-2
	CELF5	ENST00000588350.1	TSL:1	n.*105C>G		non_coding_transcript_exon	Exon 10 of 11	ENSP00000468503.1	K7ES14

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Uncertain	0.061	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.78	T
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.76	D
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.7	L
PhyloP100		7.7
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-7.8	D
REVEL	Uncertain	0.43
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.90
MutPred		0.54		Gain of MoRF binding (P = 0)
MVP		0.32
MPC		2.8
ClinPred		1.0	D
GERP RS		4.7
Varity_R		0.86
gMVP		0.84
Mutation Taster		=56/44	polymorphism

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

Other links and lift over

dbSNP: rs865957358; hg19: chr19-3293437;