19-7963566-T-A

Variant names:

• chr19-7963566-T-A
• rs199976454
• NM_001419.3:c.898A>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001419.3(ELAVL1):​c.898A>T​(p.Met300Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ELAVL1 NM_001419.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.93

Genes affected

ELAVL1 (HGNC:3312): (ELAV like RNA binding protein 1) The protein encoded by this gene is a member of the ELAVL family of RNA-binding proteins that contain several RNA recognition motifs, and selectively bind AU-rich elements (AREs) found in the 3' untranslated regions of mRNAs. AREs signal degradation of mRNAs as a means to regulate gene expression, thus by binding AREs, the ELAVL family of proteins play a role in stabilizing ARE-containing mRNAs. This gene has been implicated in a variety of biological processes and has been linked to a number of diseases, including cancer. It is highly expressed in many cancers, and could be potentially useful in cancer diagnosis, prognosis, and therapy. [provided by RefSeq, Sep 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3767761).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELAVL1	NM_001419.3	c.898A>T	p.Met300Leu	missense_variant	Exon 6 of 6	ENST00000407627.7	NP_001410.2
ELAVL1	XM_047438383.1	c.979A>T	p.Met327Leu	missense_variant	Exon 6 of 6		XP_047294339.1
ELAVL1	XM_047438384.1	c.*213A>T		3_prime_UTR_variant	Exon 5 of 5		XP_047294340.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELAVL1	ENST00000407627.7	c.898A>T	p.Met300Leu	missense_variant	Exon 6 of 6	1	NM_001419.3	ENSP00000385269.1
ELAVL1	ENST00000596459.5	c.898A>T	p.Met300Leu	missense_variant	Exon 6 of 6	2		ENSP00000472197.1
ELAVL1	ENST00000596154.5	c.185-1954A>T		intron_variant	Intron 2 of 2	3		ENSP00000471011.1
ELAVL1	ENST00000593807.1	c.*277A>T		downstream_gene_variant		3		ENSP00000470727.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 09, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.898A>T (p.M300L) alteration is located in exon 6 (coding exon 5) of the ELAVL1 gene. This alteration results from a A to T substitution at nucleotide position 898, causing the methionine (M) at amino acid position 300 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	Benign	0.20
BayesDel_addAF	Benign	0.0095	T
BayesDel_noAF	Benign	-0.22
CADD	Pathogenic	26
DANN	Benign	0.95
DEOGEN2	Benign	0.16	T;T
Eigen	Benign	-0.16
Eigen_PC	Benign	0.12
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	.;D
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.38	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-1.0	N;N
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.57	N;.
REVEL	Benign	0.19
Sift	Benign	0.41	T;.
Sift4G	Benign	0.56	T;T
Polyphen		0.0040	B;B
Vest4		0.57
MutPred		0.49		Loss of catalytic residue at M300 (P = 0.0545);Loss of catalytic residue at M300 (P = 0.0545);
MVP		0.83
MPC		1.5
ClinPred		0.71	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.45
gMVP		0.70

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

Other links and lift over

dbSNP: rs199976454; hg19: chr19-8028450;