rs2080005478

Variant names:

• chr19-3273878-C-T
• rs2080005478
• NM_021938.4:c.349C>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.349C>T​(p.Arg117Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,260 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: CELF5 NM_021938.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.02
• 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, 0.769

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.349C>T	p.Arg117Trp	missense	Exon 3 of 13	NP_068757.2
	CELF5	NM_001172673.2		c.349C>T	p.Arg117Trp	missense	Exon 3 of 12	NP_001166144.1	Q8N6W0-2
	CELF5	NR_033342.2		n.431C>T		non_coding_transcript_exon	Exon 3 of 13

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELF5	ENST00000292672.7	TSL:1 MANE Select	c.349C>T	p.Arg117Trp	missense	Exon 3 of 13	ENSP00000292672.1	Q8N6W0-1
	CELF5	ENST00000541430.6	TSL:1	c.349C>T	p.Arg117Trp	missense	Exon 3 of 12	ENSP00000443498.1	Q8N6W0-2
	CELF5	ENST00000872552.1		c.349C>T	p.Arg117Trp	missense	Exon 3 of 13	ENSP00000542611.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461260 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726900

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111522

Other (OTH) AF: 0.00 AC: 0 AN: 60364

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

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	Pathogenic	0.88
BayesDel_addAF	Uncertain	0.078	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	31
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.40	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Uncertain	0.16	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Benign	-0.40	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		3.0
PrimateAI	Pathogenic	0.92	D
PROVEAN	Pathogenic	-7.5	D
REVEL	Benign	0.28
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.98	D
Vest4		0.82
MutPred		0.52		Loss of disorder (P = 0.0013)
MVP		0.41
MPC		1.7
ClinPred		1.0	D
GERP RS		3.7
Varity_R		0.82
gMVP		0.97
Mutation Taster		=58/42	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: rs2080005478; hg19: chr19-3273876;