Variant chr14-88615826-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_183387.3(EML5):c.5926C>T(p.Pro1976Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000137 in 1,459,550 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

EML5
NM_183387.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.04

Variant links:

Genes affected

EML5 (HGNC:18197): (EMAP like 5) Predicted to enable microtubule binding activity. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

EML5 links:

ZC3H14 (HGNC:20509): (zinc finger CCCH-type containing 14) The protein encoded by this gene is a poly(A)-binding protein that can affect gene expression and poly(A) tail length. The encoded protein may influence mRNA stability, nuclear export, and translation. [provided by RefSeq, May 2016]

ZC3H14 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21326676).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EML5	NM_183387.3 link	c.5926C>T	p.Pro1976Ser	missense_variant	44/44	ENST00000554922.6	NP_899243.1	Q05BV3-5
ZC3H14	NM_024824.5 link	c.*4075G>A		3_prime_UTR_variant	17/17	ENST00000251038.10	NP_079100.2	Q6PJT7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EML5	ENST00000554922.6 link	c.5926C>T	p.Pro1976Ser	missense_variant	44/44	5	NM_183387.3	ENSP00000451998.1		Q05BV3-5
ZC3H14	ENST00000251038.10 link	c.*4075G>A		3_prime_UTR_variant	17/17	1	NM_024824.5	ENSP00000251038.5		Q6PJT7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000137

AC:

AN:

1459550

Hom.:

Cov.:

AF XY:

0.0000152

AC XY:

AN XY:

725656

show subpopulations

Gnomad4 AFR exome

AF:

0.000359

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Sep 11, 2024

The c.5926C>T (p.P1976S) alteration is located in exon 44 (coding exon 44) of the EML5 gene. This alteration results from a C to T substitution at nucleotide position 5926, causing the proline (P) at amino acid position 1976 to be replaced by a serine (S). 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

0.076

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.013

.;T

Eigen

Benign

0.051

Eigen_PC

Uncertain

0.22

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.58

T;T

M_CAP

Benign

0.0095

MetaRNN

Benign

0.21

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.4

.;L

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.50

N;N

REVEL

Benign

0.072

Sift

Uncertain

0.014

D;D

Sift4G

Benign

0.10

T;T

Polyphen

0.020

.;B

Vest4

0.15

MutPred

0.42

.;Gain of catalytic residue at P1968 (P = 0);

MVP

0.55

MPC

0.28

ClinPred

0.74

GERP RS

5.0

Varity_R

0.10

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