19-3224830-C-A

Variant names:

• chr19-3224830-C-A
• rs759584916
• NM_021938.4:c.91C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021938.4(CELF5):​c.91C>A​(p.Pro31Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000253 in 1,580,994 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. 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. P31S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CELF5 NM_021938.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.34
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10571879).

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>A	p.Pro31Thr	missense	Exon 1 of 13	NP_068757.2
	CELF5	NM_001172673.2		c.91C>A	p.Pro31Thr	missense	Exon 1 of 12	NP_001166144.1	Q8N6W0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELF5	ENST00000292672.7	TSL:1 MANE Select	c.91C>A	p.Pro31Thr	missense	Exon 1 of 13	ENSP00000292672.1	Q8N6W0-1
	CELF5	ENST00000541430.6	TSL:1	c.91C>A	p.Pro31Thr	missense	Exon 1 of 12	ENSP00000443498.1	Q8N6W0-2
	CELF5	ENST00000872552.1		c.91C>A	p.Pro31Thr	missense	Exon 1 of 13	ENSP00000542611.1

Frequencies

GnomAD3 genomes AF: 0.00000661 AC: 1 AN: 151276 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000210 AC: 3 AN: 1429718 Hom.: 0 Cov.: 31 AF XY: 0.00000282 AC XY: 2 AN XY: 708816

African (AFR) AF: 0.0000619 AC: 2 AN: 32322

American (AMR) AF: 0.00 AC: 0 AN: 39748

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25360

East Asian (EAS) AF: 0.00 AC: 0 AN: 37560

South Asian (SAS) AF: 0.00 AC: 0 AN: 82364

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50062

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5620

European-Non Finnish (NFE) AF: 9.11e-7 AC: 1 AN: 1097572

Other (OTH) AF: 0.00 AC: 0 AN: 59110

GnomAD4 genome AF: 0.00000661 AC: 1 AN: 151276 Hom.: 0 Cov.: 30 AF XY: 0.0000135 AC XY: 1 AN XY: 73844

African (AFR) AF: 0.0000242 AC: 1 AN: 41340

American (AMR) AF: 0.00 AC: 0 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3446

East Asian (EAS) AF: 0.00 AC: 0 AN: 5130

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67592

Other (OTH) AF: 0.00 AC: 0 AN: 2078

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.030	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.54	T
M_CAP	Pathogenic	0.43	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L
PhyloP100		1.3
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.61	N
REVEL	Benign	0.040
Sift	Benign	0.057	T
Sift4G	Benign	0.19	T
Polyphen		0.0080	B
Vest4		0.13
MVP		0.14
MPC		1.5
ClinPred		0.058	T
GERP RS		1.2
PromoterAI		0.0060	Neutral
Varity_R		0.053
gMVP		0.33
Mutation Taster		=74/26	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: rs759584916; hg19: chr19-3224828;