15-72290008-A-C

Position:

• chr15-72290008-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The ENST00000287202.10(CELF6):​c.534T>G​(p.Phe178Leu) variant causes a missense change involving the alteration of a non-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: CELF6 ENST00000287202.10 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.24

Genes affected

CELF6 (HGNC:14059): (CUGBP Elav-like family member 6) 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]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.859

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CELF6	NM_052840.5	c.534T>G	p.Phe178Leu	missense_variant	5/13	ENST00000287202.10	NP_443072.3
CELF6	NM_001172684.2	c.534T>G	p.Phe178Leu	missense_variant	5/12		NP_001166155.1
CELF6	NM_001172685.2	c.189T>G	p.Phe63Leu	missense_variant	4/11		NP_001166156.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CELF6	ENST00000287202.10	c.534T>G	p.Phe178Leu	missense_variant	5/13	1	NM_052840.5	ENSP00000287202	P1
	ENST00000570175.1	n.165+10977A>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2022

The c.534T>G (p.F178L) alteration is located in exon 5 (coding exon 5) of the CELF6 gene. This alteration results from a T to G substitution at nucleotide position 534, causing the phenylalanine (F) at amino acid position 178 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T;.;.;.
Eigen	Benign	0.11
Eigen_PC	Benign	0.049
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.84	.;T;T;T
M_CAP	Benign	0.034	D
MetaRNN	Pathogenic	0.86	D;D;D;D
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.8	M;.;.;M
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-5.4	D;D;D;D
REVEL	Benign	0.27
Sift	Uncertain	0.0090	D;D;D;D
Sift4G	Uncertain	0.013	D;D;D;D
Polyphen		0.71	P;.;P;.
Vest4		0.73
MutPred		0.88		Loss of methylation at K174 (P = 0.095);.;.;Loss of methylation at K174 (P = 0.095);
MVP		0.61
MPC		1.9
ClinPred		0.99	D
GERP RS		0.020
Varity_R		0.66
gMVP		0.94

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-72582349;