Variant 18-51196939-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_016626.5(MEX3C):c.382G>A(p.Glu128Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000437 in 1,544,282 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00049 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00043 ( 1 hom. )

Consequence

MEX3C
NM_016626.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.739

Variant links:

Genes affected

MEX3C (HGNC:28040): (mex-3 RNA binding family member C) This gene encodes a member of a family of proteins with two K homology (KH) RNA-binding domains and a C-terminal RING-finger domain. The protein interacts with mRNA via the KH domains, and the protein shuttles between the nucleus and cytoplasm. Polymorphisms in this gene may contribute to hypertension. [provided by RefSeq, Oct 2009]

MEX3C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04107198).

BS2

High AC in GnomAd4 at 74 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEX3C	NM_016626.5 linkuse as main transcript	c.382G>A	p.Glu128Lys	missense_variant	1/2	ENST00000406189.4
MEX3C	XM_047437540.1 linkuse as main transcript	c.382G>A	p.Glu128Lys	missense_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEX3C	ENST00000406189.4 linkuse as main transcript	c.382G>A	p.Glu128Lys	missense_variant	1/2	1	NM_016626.5	P1
MEX3C	ENST00000591040.2 linkuse as main transcript	c.-107-19363G>A		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.000487

AC:

AN:

151950

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000459

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000853

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000292

AC:

AN:

140648

Hom.:

AF XY:

0.000279

AC XY:

AN XY:

75374

show subpopulations

Gnomad AFR exome

AF:

0.000296

Gnomad AMR exome

AF:

0.000369

Gnomad ASJ exome

AF:

0.000243

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000538

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000432

AC:

601

AN:

1392224

Hom.:

Cov.:

AF XY:

0.000435

AC XY:

299

AN XY:

686866

show subpopulations

Gnomad4 AFR exome

AF:

0.0000648

Gnomad4 AMR exome

AF:

0.000422

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000253

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000508

Gnomad4 OTH exome

AF:

0.000536

GnomAD4 genome

AF:

0.000487

AC:

AN:

152058

Hom.:

Cov.:

AF XY:

0.000390

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.000853

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000478

Hom.:

Bravo

AF:

0.000495

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000680

AC:

ExAC

AF:

0.000119

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

Nov 12, 2021

The c.382G>A (p.E128K) alteration is located in exon 1 (coding exon 1) of the MEX3C gene. This alteration results from a G to A substitution at nucleotide position 382, causing the glutamic acid (E) at amino acid position 128 to be replaced by a lysine (K). 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

0.17

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.44

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.051

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.64

M_CAP

Pathogenic

0.38

MetaRNN

Benign

0.041

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

MutationTaster

Benign

0.88

PrimateAI

Pathogenic

0.94

PROVEAN

Benign

-0.40

REVEL

Benign

0.032

Sift

Pathogenic

0.0

Sift4G

Benign

0.42

Polyphen

0.075

Vest4

0.22

MVP

0.46

MPC

0.80

ClinPred

0.12

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.28

Splicing

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