Variant 14-88618720-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_183387.3(EML5):c.5468T>C(p.Ile1823Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,458,486 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

EML5
NM_183387.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.88

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.2778139).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EML5	NM_183387.3 linkuse as main transcript	c.5468T>C	p.Ile1823Thr	missense_variant	40/44	ENST00000554922.6
ZC3H14	NM_024824.5 linkuse as main transcript	c.*6969A>G		3_prime_UTR_variant	17/17	ENST00000251038.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EML5	ENST00000554922.6 linkuse as main transcript	c.5468T>C	p.Ile1823Thr	missense_variant	40/44	5	NM_183387.3	P4	Q05BV3-5
ZC3H14	ENST00000251038.10 linkuse as main transcript	c.*6969A>G		3_prime_UTR_variant	17/17	1	NM_024824.5	P3	Q6PJT7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1458486

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725106

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000828

AC:

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 26, 2022

The c.5468T>C (p.I1823T) alteration is located in exon 40 (coding exon 40) of the EML5 gene. This alteration results from a T to C substitution at nucleotide position 5468, causing the isoleucine (I) at amino acid position 1823 to be replaced by a threonine (T). 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

0.16

BayesDel_addAF

Benign

-0.075

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.038

.;T;.

Eigen

Benign

-0.10

Eigen_PC

Benign

0.081

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.86

D;D;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.28

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

.;L;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.4

N;N;N

REVEL

Benign

0.051

Sift

Benign

0.21

T;T;T

Sift4G

Benign

0.27

T;T;.

Polyphen

0.0020

.;B;.

Vest4

0.62

MutPred

0.59

.;Gain of catalytic residue at R1814 (P = 2e-04);.;

MVP

0.64

MPC

0.35

ClinPred

0.65

GERP RS

4.6

Varity_R

0.15

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