chr19-11454776-C-T

Variant names:

• chr19-11454776-C-T
• NM_001420.4:c.854G>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001420.4(ELAVL3):​c.854G>A​(p.Cys285Tyr) variant causes a missense change involving the alteration of a 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: ELAVL3 NM_001420.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.45
• Publications: 0 publications found

Genes affected

ELAVL3 (HGNC:3314): (ELAV like RNA binding protein 3) A member of the ELAVL protein family, ELAV-like 3 is a neural-specific RNA-binding protein which contains three RNP-type RNA recognition motifs. The observation that ELAVL3 is one of several Hu antigens (neuronal-specific RNA-binding proteins) recognized by the anti-Hu serum antibody present in sera from patients with paraneoplastic encephalomyelitis and sensory neuronopathy (PEM/PSN) suggests it has a role in neurogenesis. Two alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.899

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001420.4. 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
	ELAVL3	NM_001420.4	MANE Select	c.854G>A	p.Cys285Tyr	missense	Exon 7 of 7	NP_001411.2
	ELAVL3	NM_032281.3		c.833G>A	p.Cys278Tyr	missense	Exon 7 of 7	NP_115657.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELAVL3	ENST00000359227.8	TSL:3 MANE Select	c.854G>A	p.Cys285Tyr	missense	Exon 7 of 7	ENSP00000352162.1	Q14576-1
	ELAVL3	ENST00000897487.1		c.851G>A	p.Cys284Tyr	missense	Exon 7 of 7	ENSP00000567546.1
	ELAVL3	ENST00000438662.6	TSL:5	c.833G>A	p.Cys278Tyr	missense	Exon 7 of 7	ENSP00000390878.1	Q14576-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

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	1.0
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.54	D
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.90	D
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.7	L
PhyloP100		7.5
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-10	D
REVEL	Uncertain	0.60
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.038	D
Polyphen		0.86	P
Vest4		0.89
MutPred		0.69		Loss of sheet (P = 0.0817)
MVP		0.85
MPC		2.8
ClinPred		1.0	D
GERP RS		4.7
Varity_R		0.96
gMVP		0.95
Mutation Taster		=21/79	disease causing

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

hg19: chr19-11565591;