rs757598407

Variant names:

• chr1-151707154-G-A
• rs757598407
• NM_007185.7:c.913C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-151707154-G-A
• chr1-151707154-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_007185.7(CELF3):​c.913C>T​(p.Pro305Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000205 in 1,508,662 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: CELF3 NM_007185.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.00
• Publications: 0 publications found

Genes affected

CELF3 (HGNC:11967): (CUGBP Elav-like family member 3) Members of the CELF/BRUNOL protein family 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. Multiple alternatively spliced transcript variants encoding different isoforms have been identified in this gene. [provided by RefSeq, Feb 2010]

ENSG00000227045 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32623369).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007185.7. 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
	CELF3	NM_007185.7	MANE Select	c.913C>T	p.Pro305Ser	missense	Exon 8 of 13	NP_009116.3
	CELF3	NM_001291106.2		c.913C>T	p.Pro305Ser	missense	Exon 8 of 13	NP_001278035.1	Q5SZQ8-2
	CELF3	NM_001291107.2		c.910C>T	p.Pro304Ser	missense	Exon 8 of 13	NP_001278036.1	Q5SZQ8-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELF3	ENST00000290583.9	TSL:1 MANE Select	c.913C>T	p.Pro305Ser	missense	Exon 8 of 13	ENSP00000290583.4	Q5SZQ8-1
	CELF3	ENST00000290585.8	TSL:1	c.772+353C>T		intron	N/A	ENSP00000290585.4	Q5SZQ8-4
	CELF3	ENST00000420342.1	TSL:5	c.913C>T	p.Pro305Ser	missense	Exon 9 of 14	ENSP00000402503.1	H0Y623

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152226 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000241

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000152 AC: 2 AN: 131810 AF XY: 0.0000286

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000331

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000206 AC: 28 AN: 1356436 Hom.: 0 Cov.: 32 AF XY: 0.0000180 AC XY: 12 AN XY: 666720

African (AFR) AF: 0.00 AC: 0 AN: 29588

American (AMR) AF: 0.00 AC: 0 AN: 22318

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21730

East Asian (EAS) AF: 0.00 AC: 0 AN: 36170

South Asian (SAS) AF: 0.00 AC: 0 AN: 70036

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49672

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5470

European-Non Finnish (NFE) AF: 0.0000244 AC: 26 AN: 1065358

Other (OTH) AF: 0.0000357 AC: 2 AN: 56094

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152226 Hom.: 0 Cov.: 34 AF XY: 0.0000403 AC XY: 3 AN XY: 74368

African (AFR) AF: 0.0000241 AC: 1 AN: 41464

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.0000167 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Neuromuscular disease (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.54	D
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		4.0
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.12
Sift	Benign	0.18	T
Sift4G	Benign	0.19	T
Polyphen		0.38	B
Vest4		0.60
MutPred		0.31		Gain of relative solvent accessibility (P = 0.0082)
MVP		0.25
MPC		0.35
ClinPred		0.74	D
GERP RS		3.9
Varity_R		0.21
gMVP		0.55
Mutation Taster		=61/39	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: rs757598407; hg19: chr1-151679630;