Variant 14-88618739-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_183387.3(EML5):c.5449G>C(p.Gly1817Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,454,690 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

EML5
NM_183387.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.46

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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.846

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EML5	NM_183387.3 linkuse as main transcript	c.5449G>C	p.Gly1817Arg	missense_variant	40/44	ENST00000554922.6	NP_899243.1
ZC3H14	NM_024824.5 linkuse as main transcript	c.*6988C>G		3_prime_UTR_variant	17/17	ENST00000251038.10	NP_079100.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EML5	ENST00000554922.6 linkuse as main transcript	c.5449G>C	p.Gly1817Arg	missense_variant	40/44	5	NM_183387.3	ENSP00000451998	P4	Q05BV3-5
ZC3H14	ENST00000251038.10 linkuse as main transcript	c.*6988C>G		3_prime_UTR_variant	17/17	1	NM_024824.5	ENSP00000251038	P3	Q6PJT7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1454690

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722790

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:

9.02e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

May 23, 2023

The c.5449G>C (p.G1817R) alteration is located in exon 40 (coding exon 40) of the EML5 gene. This alteration results from a G to C substitution at nucleotide position 5449, causing the glycine (G) at amino acid position 1817 to be replaced by an arginine (R). 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

0.93

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Uncertain

0.090

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.21

.;T

Eigen

Pathogenic

0.86

Eigen_PC

Pathogenic

0.84

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.98

D;D

M_CAP

Benign

0.069

MetaRNN

Pathogenic

0.85

D;D

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.8

.;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.80

PROVEAN

Pathogenic

-4.7

D;D

REVEL

Uncertain

0.58

Sift

Uncertain

0.0060

D;D

Sift4G

Uncertain

0.0050

D;D

Polyphen

1.0

.;D

Vest4

0.92

MutPred

0.56

.;Gain of catalytic residue at L1812 (P = 2e-04);

MVP

0.55

MPC

1.1

ClinPred

1.0

GERP RS

5.7

Varity_R

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.19

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over