Genetic Variant NM_016626.5:c.251C>T (chr18-51197070-G-A) – 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.251C>T(p.Ala84Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000424 in 1,367,432 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

MEX3C
NM_016626.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0650

Publications

0 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=0.017665625).

BS2

High AC in GnomAdExome4 at 54 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.251C>T	p.Ala84Val	missense	Exon 1 of 2	NP_057710.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEX3C	ENST00000406189.4	TSL:1 MANE Select	c.251C>T	p.Ala84Val	missense	Exon 1 of 2	ENSP00000385610.3	Q5U5Q3
	MEX3C	ENST00000591040.2	TSL:2	c.-107-19494C>T		intron	N/A	ENSP00000502049.1	A0A6Q8PG18

Frequencies

GnomAD3 genomes

AF:

0.0000268

AC:

AN:

149462

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000831

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000610

AC:

AN:

16406

AF XY:

0.000102

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000443

AC:

AN:

1217970

Hom.:

Cov.:

AF XY:

0.0000522

AC XY:

AN XY:

593754

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23852

American (AMR)

AF:

0.0000753

AC:

AN:

13284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17328

East Asian (EAS)

AF:

0.00

AC:

AN:

26984

South Asian (SAS)

AF:

0.000558

AC:

AN:

55598

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29478

Middle Eastern (MID)

AF:

0.000592

AC:

AN:

3376

European-Non Finnish (NFE)

AF:

0.0000140

AC:

AN:

998622

Other (OTH)

AF:

0.000121

AC:

AN:

49448

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000268

AC:

AN:

149462

Hom.:

Cov.:

AF XY:

0.0000274

AC XY:

AN XY:

72890

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41106

American (AMR)

AF:

0.00

AC:

AN:

15034

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3438

East Asian (EAS)

AF:

0.00

AC:

AN:

5096

South Asian (SAS)

AF:

0.000831

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9678

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67018

Other (OTH)

AF:

0.00

AC:

AN:

2062

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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:

0.00

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.000882

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

0.13

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.034

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.53

M_CAP

Benign

0.041

MetaRNN

Benign

0.018

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

0.065

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.080

REVEL

Benign

0.041

Sift

Benign

0.13

Sift4G

Benign

0.29

Polyphen

0.0090

Vest4

0.041

MutPred

0.26

Gain of MoRF binding (P = 0.0681)

MVP

0.26

MPC

0.71

ClinPred

0.13

GERP RS

1.2

PromoterAI

0.0097

Neutral

(source)

Varity_R

0.062

Mutation Taster

=96/4

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