19-11466796-C-G

Position:

chr19-11466796-C-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001420.4(ELAVL3):c.41G>C(p.Gly14Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000863 in 1,611,586 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: 𝑓 0.000053 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000090 ( 0 hom. )

Consequence

ELAVL3
NM_001420.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.22

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:

ENSG00000267477 (HGNC:):

ENSG00000267477 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06547719).

BS2

High AC in GnomAd4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELAVL3	NM_001420.4 linkuse as main transcript	c.41G>C	p.Gly14Ala	missense_variant	2/7	ENST00000359227.8	NP_001411.2	Q14576-1
ELAVL3	NM_032281.3 linkuse as main transcript	c.41G>C	p.Gly14Ala	missense_variant	2/7		NP_115657.2	Q14576-2
ELAVL3	XM_011527778.3 linkuse as main transcript	c.38G>C	p.Gly13Ala	missense_variant	2/7		XP_011526080.1
ELAVL3	XM_024451413.1 linkuse as main transcript	c.38G>C	p.Gly13Ala	missense_variant	2/7		XP_024307181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ELAVL3	ENST00000359227.8 linkuse as main transcript	c.41G>C	p.Gly14Ala	missense_variant	2/7	3	NM_001420.4	ENSP00000352162.1	Q14576-1
ENSG00000267477	ENST00000585656.1 linkuse as main transcript	n.501G>C		non_coding_transcript_exon_variant	4/5	5		ENSP00000466387.1	K7EM74
ELAVL3	ENST00000438662.6 linkuse as main transcript	c.41G>C	p.Gly14Ala	missense_variant	2/7	5		ENSP00000390878.1	Q14576-2
ELAVL3	ENST00000588853.1 linkuse as main transcript	c.41G>C	p.Gly14Ala	missense_variant	2/3	3		ENSP00000467314.1	K7EPB5

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000578

AC:

AN:

242364

Hom.:

AF XY:

0.0000532

AC XY:

AN XY:

131570

show subpopulations

Gnomad AFR exome

AF:

0.0000651

Gnomad AMR exome

AF:

0.000208

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000331

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000461

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000898

AC:

131

AN:

1459390

Hom.:

Cov.:

AF XY:

0.0000937

AC XY:

AN XY:

725904

show subpopulations

Gnomad4 AFR exome

AF:

0.000150

Gnomad4 AMR exome

AF:

0.000159

Gnomad4 ASJ exome

AF:

0.0000384

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000999

Gnomad4 OTH exome

AF:

0.0000830

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000450

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 28, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.13

T;.;.

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.48

LIST_S2

Uncertain

0.88

D;D;D

M_CAP

Benign

0.0026

MetaRNN

Benign

0.065

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

N;N;.

PrimateAI

Uncertain

0.74

PROVEAN

Benign

0.38

N;N;.

REVEL

Benign

0.042

Sift

Benign

0.15

T;T;.

Sift4G

Benign

0.35

T;T;.

Polyphen

0.0

B;B;.

Vest4

0.22

MVP

0.30

MPC

1.1

ClinPred

0.070

GERP RS

3.5

Varity_R

0.054

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.18

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