Variant 19-11454818-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001420.4(ELAVL3):c.812C>T(p.Ala271Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000686 in 1,458,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

ELAVL3
NM_001420.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.84

Variant links:

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]

ELAVL3 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.16503751).

BS2

High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELAVL3	NM_001420.4 linkuse as main transcript	c.812C>T	p.Ala271Val	missense_variant	7/7	ENST00000359227.8	NP_001411.2	Q14576-1
ELAVL3	NM_032281.3 linkuse as main transcript	c.791C>T	p.Ala264Val	missense_variant	7/7		NP_115657.2	Q14576-2
ELAVL3	XM_011527778.3 linkuse as main transcript	c.809C>T	p.Ala270Val	missense_variant	7/7		XP_011526080.1
ELAVL3	XM_024451413.1 linkuse as main transcript	c.788C>T	p.Ala263Val	missense_variant	7/7		XP_024307181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELAVL3	ENST00000359227.8 linkuse as main transcript	c.812C>T	p.Ala271Val	missense_variant	7/7	3	NM_001420.4	ENSP00000352162.1		Q14576-1
ELAVL3	ENST00000438662.6 linkuse as main transcript	c.791C>T	p.Ala264Val	missense_variant	7/7	5		ENSP00000390878.1		Q14576-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000410

AC:

AN:

243782

Hom.:

AF XY:

0.00

AC XY:

AN XY:

132326

show subpopulations

Gnomad AFR exome

AF:

0.0000629

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000686

AC:

AN:

1458042

Hom.:

Cov.:

AF XY:

0.00000552

AC XY:

AN XY:

725230

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 04, 2024

The c.812C>T (p.A271V) alteration is located in exon 7 (coding exon 7) of the ELAVL3 gene. This alteration results from a C to T substitution at nucleotide position 812, causing the alanine (A) at amino acid position 271 to be replaced by a valine (V). 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

Benign

0.15

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

T;.

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.0018

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.68

T;D

M_CAP

Benign

0.0088

MetaRNN

Benign

0.17

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;.

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.16

Sift

Benign

0.34

T;T

Sift4G

Benign

0.18

T;T

Polyphen

0.022

B;B

Vest4

0.18

MutPred

0.32

Loss of disorder (P = 0.0685);.;

MVP

0.50

MPC

1.0

ClinPred

0.24

GERP RS

4.8

Varity_R

0.18

gMVP

0.85

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over