Genetic Variant MEX3D:p.Thr510Ile (chr19-1555990-G-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4

The NM_203304.4(MEX3D):c.1529C>T(p.Thr510Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000172 in 1,199,998 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

MEX3D
NM_203304.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.54

Variant links:

Genes affected

MEX3D (HGNC:16734): (mex-3 RNA binding family member D) Enables mRNA 3'-UTR AU-rich region binding activity. Located in nucleus and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MEX3D links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM1

In a modified_residue Phosphothreonine (size 0) in uniprot entity MEX3D_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32047832).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEX3D	NM_203304.4 link	c.1529C>T	p.Thr510Ile	missense_variant	Exon 2 of 2	ENST00000402693.5	NP_976049.3	Q86XN8-1
MEX3D	NM_001174118.2 link	c.1529C>T	p.Thr510Ile	missense_variant	Exon 2 of 3		NP_001167589.1	Q86XN8-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEX3D	ENST00000402693.5 link	c.1529C>T	p.Thr510Ile	missense_variant	Exon 2 of 2	1	NM_203304.4	ENSP00000384398.3		Q86XN8-1
MEX3D	ENST00000605173.2 link	c.1001C>T	p.Thr334Ile	missense_variant	Exon 2 of 3	1		ENSP00000475059.1		S4R446

Frequencies

GnomAD3 genomes

AF:

0.000223

AC:

AN:

148218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000244

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00127

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:

0.000196

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000164

AC:

173

AN:

1051780

Hom.:

Cov.:

AF XY:

0.000155

AC XY:

AN XY:

502386

show subpopulations

Gnomad4 AFR exome

AF:

0.000151

Gnomad4 AMR exome

AF:

0.000841

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:

0.000178

Gnomad4 OTH exome

AF:

0.000126

GnomAD4 genome

AF:

0.000223

AC:

AN:

148218

Hom.:

Cov.:

AF XY:

0.000249

AC XY:

AN XY:

72184

show subpopulations

Gnomad4 AFR

AF:

0.0000244

Gnomad4 AMR

AF:

0.00127

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000196

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000234

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1529C>T (p.T510I) alteration is located in exon 2 (coding exon 2) of the MEX3D gene. This alteration results from a C to T substitution at nucleotide position 1529, causing the threonine (T) at amino acid position 510 to be replaced by an isoleucine (I). 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

0.23

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.042

T;T

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.32

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.68

T;T

M_CAP

Pathogenic

0.61

MetaRNN

Benign

0.32

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.6

M;.

PrimateAI

Pathogenic

0.92

PROVEAN

Uncertain

-3.0

D;.

REVEL

Benign

0.050

Sift

Uncertain

0.0020

D;.

Sift4G

Uncertain

0.057

T;T

Polyphen

0.51

P;.

Vest4

0.068

MutPred

0.27

Loss of phosphorylation at T510 (P = 0.0047);.;

MVP

0.30

ClinPred

0.96

GERP RS

3.2

Varity_R

0.20

gMVP

0.36

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