Genetic Variant NM_016626.5:c.382G>A (chr18-51196939-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

1 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

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

BS2

High AC in GnomAd4 at 74 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016626.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEX3C	NM_016626.5	MANE Select	c.382G>A	p.Glu128Lys	missense	Exon 1 of 2	NP_057710.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MEX3C	ENST00000406189.4	TSL:1 MANE Select	c.382G>A	p.Glu128Lys	missense	Exon 1 of 2	ENSP00000385610.3	Q5U5Q3
MEX3C	ENST00000591040.2	TSL:2	c.-107-19363G>A		intron	N/A	ENSP00000502049.1	A0A6Q8PG18
MEX3C	ENST00000592416.1	TSL:6	c.-180G>A		upstream_gene	N/A	ENSP00000468078.1	K7ER23

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

GnomAD2 exomes

AF:

0.000292

AC:

AN:

140648

AF XY:

0.000279

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 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

African (AFR)

AF:

0.0000648

AC:

AN:

30862

American (AMR)

AF:

0.000422

AC:

AN:

35568

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25082

East Asian (EAS)

AF:

0.00

AC:

AN:

35408

South Asian (SAS)

AF:

0.0000253

AC:

AN:

79008

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45090

Middle Eastern (MID)

AF:

0.000555

AC:

AN:

5406

European-Non Finnish (NFE)

AF:

0.000508

AC:

548

AN:

1077972

Other (OTH)

AF:

0.000536

AC:

AN:

57828

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

102

136

170

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000487

AC:

AN:

152058

Hom.:

Cov.:

AF XY:

0.000390

AC XY:

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.000144

AC:

AN:

41542

American (AMR)

AF:

0.000458

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5114

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.000189

AC:

AN:

10556

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.000853

AC:

AN:

67956

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000416

Hom.:

Bravo

AF:

0.000495

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000680

AC:

ExAC

AF:

0.000119

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.44

CADD

Uncertain

(source)

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

PhyloP100

0.74

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

PromoterAI

-0.14

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.28

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over