19-1555853-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_203304.4(MEX3D):​c.1666G>A​(p.Ala556Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000525 in 1,333,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000051 ( 0 hom. )

Consequence

MEX3D
NM_203304.4 missense

Scores

1
1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.661
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.0384911).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MEX3DNM_203304.4 linkc.1666G>A p.Ala556Thr missense_variant Exon 2 of 2 ENST00000402693.5 NP_976049.3 Q86XN8-1
MEX3DNM_001174118.2 linkc.1666G>A p.Ala556Thr missense_variant Exon 2 of 3 NP_001167589.1 Q86XN8-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MEX3DENST00000402693.5 linkc.1666G>A p.Ala556Thr missense_variant Exon 2 of 2 1 NM_203304.4 ENSP00000384398.3 Q86XN8-1
MEX3DENST00000605173.2 linkc.1138G>A p.Ala380Thr missense_variant Exon 2 of 3 1 ENSP00000475059.1 S4R446

Frequencies

GnomAD3 genomes
AF:
0.00000661
AC:
1
AN:
151206
Hom.:
0
Cov.:
32
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:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000148
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000508
AC:
6
AN:
1181866
Hom.:
0
Cov.:
35
AF XY:
0.00000701
AC XY:
4
AN XY:
570326
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000392
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000838
GnomAD4 genome
AF:
0.00000661
AC:
1
AN:
151206
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
73842
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000148
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 14, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1666G>A (p.A556T) alteration is located in exon 2 (coding exon 2) of the MEX3D gene. This alteration results from a G to A substitution at nucleotide position 1666, causing the alanine (A) at amino acid position 556 to be replaced by a threonine (T). 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
0.068
BayesDel_addAF
Benign
-0.40
T
BayesDel_noAF
Benign
-0.81
CADD
Benign
0.85
DANN
Benign
0.80
DEOGEN2
Benign
0.0025
T;T
Eigen
Benign
-1.7
Eigen_PC
Benign
-1.7
FATHMM_MKL
Benign
0.018
N
LIST_S2
Benign
0.38
T;T
M_CAP
Uncertain
0.15
D
MetaRNN
Benign
0.038
T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
-0.69
N;.
PrimateAI
Pathogenic
0.81
D
PROVEAN
Benign
0.40
N;.
REVEL
Benign
0.025
Sift
Benign
0.86
T;.
Sift4G
Benign
0.93
T;T
Polyphen
0.0010
B;.
Vest4
0.064
MutPred
0.14
Gain of glycosylation at A556 (P = 0.0164);.;
MVP
0.081
ClinPred
0.032
T
GERP RS
-5.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.2
Varity_R
0.013
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.

Other links and lift over

dbSNP: rs1442681156; hg19: chr19-1555852; API