19-1555715-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_203304.4(MEX3D):​c.1804G>A​(p.Val602Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000719 in 1,391,216 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

MEX3D
NM_203304.4 missense

Scores

2
11
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.78
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 Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MEX3DNM_203304.4 linkc.1804G>A p.Val602Met missense_variant Exon 2 of 2 ENST00000402693.5 NP_976049.3 Q86XN8-1
MEX3DNM_001174118.2 linkc.1804G>A p.Val602Met 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.1804G>A p.Val602Met missense_variant Exon 2 of 2 1 NM_203304.4 ENSP00000384398.3 Q86XN8-1
MEX3DENST00000605173.2 linkc.1276G>A p.Val426Met missense_variant Exon 2 of 3 1 ENSP00000475059.1 S4R446

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
7.19e-7
AC:
1
AN:
1391216
Hom.:
0
Cov.:
35
AF XY:
0.00000145
AC XY:
1
AN XY:
687702
show subpopulations
Gnomad4 AFR exome
AF:
0.0000329
Gnomad4 AMR exome
AF:
0.00
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Mar 26, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1804G>A (p.V602M) 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 1804, causing the valine (V) at amino acid position 602 to be replaced by a methionine (M). 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
Uncertain
0.46
BayesDel_addAF
Uncertain
0.091
D
BayesDel_noAF
Benign
-0.11
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.030
T;T
Eigen
Uncertain
0.38
Eigen_PC
Uncertain
0.27
FATHMM_MKL
Benign
0.67
D
LIST_S2
Uncertain
0.87
D;D
M_CAP
Pathogenic
0.86
D
MetaRNN
Uncertain
0.71
D;D
MetaSVM
Uncertain
-0.16
T
MutationAssessor
Uncertain
2.5
M;.
PrimateAI
Pathogenic
0.93
D
PROVEAN
Benign
-1.6
N;.
REVEL
Uncertain
0.53
Sift
Uncertain
0.011
D;.
Sift4G
Benign
0.089
T;T
Polyphen
1.0
D;.
Vest4
0.48
MutPred
0.67
Gain of disorder (P = 0.0742);.;
MVP
0.54
ClinPred
0.89
D
GERP RS
2.7
Varity_R
0.15
gMVP
0.76

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: rs1914515178; hg19: chr19-1555714; API