NM_007185.7:c.841G>A

Variant names:

• chr1-151707226-C-T
• rs966059814
• NM_007185.7:c.841G>A

Variant summary

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

The NM_007185.7(CELF3):​c.841G>A​(p.Gly281Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000645 in 1,550,942 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 0.000026 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: CELF3 NM_007185.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.79
• Publications: 3 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2523443).

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.841G>A	p.Gly281Ser	missense	Exon 8 of 13	NP_009116.3
	CELF3	NM_001291106.2		c.841G>A	p.Gly281Ser	missense	Exon 8 of 13	NP_001278035.1	Q5SZQ8-2
	CELF3	NM_001291107.2		c.838G>A	p.Gly280Ser	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.841G>A	p.Gly281Ser	missense	Exon 8 of 13	ENSP00000290583.4	Q5SZQ8-1
	CELF3	ENST00000290585.8	TSL:1	c.772+281G>A		intron	N/A	ENSP00000290585.4	Q5SZQ8-4
	CELF3	ENST00000420342.1	TSL:5	c.841G>A	p.Gly281Ser	missense	Exon 9 of 14	ENSP00000402503.1	H0Y623

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152170 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000965

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: 0.00000429 AC: 6 AN: 1398772 Hom.: 0 Cov.: 32 AF XY: 0.00000289 AC XY: 2 AN XY: 691886

African (AFR) AF: 0.0000643 AC: 2 AN: 31102

American (AMR) AF: 0.00 AC: 0 AN: 30504

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24170

East Asian (EAS) AF: 0.00 AC: 0 AN: 36982

South Asian (SAS) AF: 0.00 AC: 0 AN: 78392

European-Finnish (FIN) AF: 0.0000199 AC: 1 AN: 50228

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5600

European-Non Finnish (NFE) AF: 0.00000277 AC: 3 AN: 1083930

Other (OTH) AF: 0.00 AC: 0 AN: 57864

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152170 Hom.: 0 Cov.: 34 AF XY: 0.0000538 AC XY: 4 AN XY: 74334

African (AFR) AF: 0.0000965 AC: 4 AN: 41442

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

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	Benign	0.069
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.48	T
Eigen	Benign	0.022
Eigen_PC	Benign	0.098
FATHMM_MKL	Benign	0.72	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		1.8
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.069
Sift	Benign	0.14	T
Sift4G	Benign	0.20	T
Polyphen		0.44	B
Vest4		0.35
MutPred		0.25		Gain of glycosylation at G281 (P = 0.0067)
MVP		0.18
MPC		0.39
ClinPred		0.96	D
GERP RS		3.9
Varity_R		0.29
gMVP		0.58
Mutation Taster		=60/40	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs966059814; hg19: chr1-151679702; COSMIC: COSV51881765; COSMIC: COSV51881765;