19-11454776-C-T

Position:

• chr19-11454776-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

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, 0.899

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELAVL3	NM_001420.4	c.854G>A	p.Cys285Tyr	missense_variant	7/7	ENST00000359227.8	NP_001411.2
ELAVL3	NM_032281.3	c.833G>A	p.Cys278Tyr	missense_variant	7/7		NP_115657.2
ELAVL3	XM_011527778.3	c.851G>A	p.Cys284Tyr	missense_variant	7/7		XP_011526080.1
ELAVL3	XM_024451413.1	c.830G>A	p.Cys277Tyr	missense_variant	7/7		XP_024307181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELAVL3	ENST00000359227.8	c.854G>A	p.Cys285Tyr	missense_variant	7/7	3	NM_001420.4	ENSP00000352162.1
ELAVL3	ENST00000438662.6	c.833G>A	p.Cys278Tyr	missense_variant	7/7	5		ENSP00000390878.1

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

Sep 22, 2023

The c.854G>A (p.C285Y) alteration is located in exon 7 (coding exon 7) of the ELAVL3 gene. This alteration results from a G to A substitution at nucleotide position 854, causing the cysteine (C) at amino acid position 285 to be replaced by a tyrosine (Y). 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	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;D
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.90	D;D
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.7	L;.
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-10	D;D
REVEL	Uncertain	0.60
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.038	D;D
Polyphen		0.86	P;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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-11565591;