chr1-50177095-G-A

Position:

• chr1-50177095-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PP2 PP3_Moderate

The NM_001144774.3(ELAVL4):​c.257G>A​(p.Ser86Asn) 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: 33)
• Consequence: ELAVL4 NM_001144774.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.60

Genes affected

ELAVL4 (HGNC:3315): (ELAV like RNA binding protein 4) Enables mRNA 3'-UTR AU-rich region binding activity; poly(A) binding activity; and pre-mRNA intronic pyrimidine-rich binding activity. Involved in 3'-UTR-mediated mRNA stabilization; RNA processing; and positive regulation of 3'-UTR-mediated mRNA stabilization. Predicted to be located in axon; cytoplasm; and dendrite. Predicted to be part of polysomal ribosome. Predicted to be active in glutamatergic synapse. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, ELAVL4
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.863

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELAVL4	NM_001144774.3	c.257G>A	p.Ser86Asn	missense_variant	3/7	ENST00000371824.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELAVL4	ENST00000371824.7	c.257G>A	p.Ser86Asn	missense_variant	3/7	1	NM_001144774.3	P4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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

Dec 21, 2023

The c.308G>A (p.S103N) alteration is located in exon 3 (coding exon 3) of the ELAVL4 gene. This alteration results from a G to A substitution at nucleotide position 308, causing the serine (S) at amino acid position 103 to be replaced by an asparagine (N). 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	0.99
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	29
DANN	Uncertain	1.0
Eigen	Pathogenic	0.88
Eigen_PC	Pathogenic	0.88
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D;D;D;D;D;D
M_CAP	Benign	0.012	T
MetaRNN	Pathogenic	0.86	D;D;D;D;D;D;D
MetaSVM	Benign	-0.63	T
MutationTaster	Benign	1.0	D;D;D;D;D;D;D
PrimateAI	Pathogenic	0.92	D
PROVEAN	Uncertain	-2.7	D;D;.;D;D;D;D
REVEL	Uncertain	0.37
Sift	Uncertain	0.0010	D;D;.;D;D;D;D
Sift4G	Uncertain	0.0020	D;D;D;D;D;D;D
Polyphen		0.99, 1.0, 1.0, 1.0	.;D;.;D;D;D;D
Vest4		0.84
MutPred		0.75		.;.;.;.;.;Loss of catalytic residue at G89 (P = 0.0822);Loss of catalytic residue at G89 (P = 0.0822);
MVP		0.67
MPC		1.7
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.94
gMVP		0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: chr1-50642767;