Variant 14-88620917-T-G 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.5212A>C(p.Asn1738His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000014 in 1,503,660 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 31)

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: 7.67

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:

ZC3H14 (HGNC:):

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=0.23652685).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EML5	NM_183387.3 linkuse as main transcript	c.5212A>C	p.Asn1738His	missense_variant	39/44	ENST00000554922.6	NP_899243.1	Q05BV3-5
ZC3H14	NM_024824.5 linkuse as main transcript	c.*9166T>G		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 linkuse as main transcript	c.5212A>C	p.Asn1738His	missense_variant	39/44	5	NM_183387.3	ENSP00000451998.1		Q05BV3-5
ZC3H14	ENST00000251038.10 linkuse as main transcript	c.*9166T>G		3_prime_UTR_variant	17/17	1	NM_024824.5	ENSP00000251038.5		Q6PJT7-1

Frequencies

GnomAD3 genomes

AF:

0.0000137

AC:

AN:

146424

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000722

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000150

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000443

AC:

AN:

112986

Hom.:

AF XY:

0.0000502

AC XY:

AN XY:

59794

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000399

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000202

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000140

AC:

AN:

1357118

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

668082

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000365

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:

0.00000843

Gnomad4 OTH exome

AF:

0.0000356

GnomAD4 genome

AF:

0.0000136

AC:

AN:

146542

Hom.:

Cov.:

AF XY:

0.0000141

AC XY:

AN XY:

71110

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000721

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000150

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ExAC

AF:

0.0000101

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

Oct 16, 2024

The c.5212A>C (p.N1738H) alteration is located in exon 39 (coding exon 39) of the EML5 gene. This alteration results from a A to C substitution at nucleotide position 5212, causing the asparagine (N) at amino acid position 1738 to be replaced by a histidine (H). 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

0.22

BayesDel_addAF

Benign

-0.0026

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.042

.;T;.

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

D;D;D

M_CAP

Benign

0.043

MetaRNN

Benign

0.24

T;T;T

MetaSVM

Benign

-0.80

MutationAssessor

Benign

1.8

.;L;.

PrimateAI

Uncertain

0.79

PROVEAN

Uncertain

-2.5

D;D;D

REVEL

Uncertain

0.30

Sift

Benign

0.57

T;T;T

Sift4G

Benign

0.19

T;T;.

Polyphen

1.0

.;D;.

Vest4

0.77

MutPred

0.40

.;Gain of catalytic residue at K1731 (P = 6e-04);.;

MVP

0.60

MPC

0.37

ClinPred

0.23

GERP RS

5.4

Varity_R

0.43

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