Genetic Variant NM_032246.6:c.1067G>A (chr15-82043803-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032246.6(MEX3B):c.1067G>A(p.Cys356Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000977 in 1,432,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000098 ( 0 hom. )

Consequence

MEX3B
NM_032246.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.307

Publications

0 publications found

Variant links:

Genes affected

MEX3B (HGNC:25297): (mex-3 RNA binding family member B) This gene encodes an RNA-binding phosphoprotein that is part of the MEX3 (muscle excess 3) family of translational regulators. The encoded protein contains N-terminal nuclear export and nuclear localization signals and is exported from the cytoplasm to the nucleus. The protein binds to RNA via two KH domains and also colocalizes with MEX3A, Dcp1A decapping factor and Argonaute proteins within P (processing) bodies. [provided by RefSeq, Oct 2012]

MEX3B links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13257906).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032246.6. 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
	MEX3B	NM_032246.6	MANE Select	c.1067G>A	p.Cys356Tyr	missense	Exon 2 of 2	NP_115622.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEX3B	ENST00000329713.5	TSL:1 MANE Select	c.1067G>A	p.Cys356Tyr	missense	Exon 2 of 2	ENSP00000329918.4	Q6ZN04-1
	MEX3B	ENST00000558133.1	TSL:6	c.*1426G>A		3_prime_UTR	Exon 1 of 1	ENSP00000456938.1	Q6ZN04-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000447

AC:

AN:

223728

AF XY:

0.00000830

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:

0.00000977

AC:

AN:

1432856

Hom.:

Cov.:

AF XY:

0.0000127

AC XY:

AN XY:

710180

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32578

American (AMR)

AF:

0.00

AC:

AN:

40684

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23924

East Asian (EAS)

AF:

0.00

AC:

AN:

39516

South Asian (SAS)

AF:

0.000123

AC:

AN:

81036

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51982

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5606

European-Non Finnish (NFE)

AF:

0.00000273

AC:

AN:

1098420

Other (OTH)

AF:

0.0000169

AC:

AN:

59110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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

Cov.:

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.00000825

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

0.11

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.054

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.70

M_CAP

Benign

0.064

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

PhyloP100

0.31

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-1.5

REVEL

Benign

0.10

Sift

Benign

0.30

Sift4G

Benign

0.60

Polyphen

0.64

Vest4

0.24

MutPred

0.24

Gain of phosphorylation at C356 (P = 0.0033)

MVP

0.32

MPC

1.1

ClinPred

0.16

GERP RS

3.8

Varity_R

0.11

gMVP

0.53

Mutation Taster

=82/18

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over