19-1555715-C-T

Variant names:

• chr19-1555715-C-T
• rs1914515178
• NM_203304.4:c.1804G>A

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.78

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]

ACMG classification

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
MEX3D	NM_203304.4	c.1804G>A	p.Val602Met	missense_variant	Exon 2 of 2	ENST00000402693.5	NP_976049.3
MEX3D	NM_001174118.2	c.1804G>A	p.Val602Met	missense_variant	Exon 2 of 3		NP_001167589.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEX3D	ENST00000402693.5	c.1804G>A	p.Val602Met	missense_variant	Exon 2 of 2	1	NM_203304.4	ENSP00000384398.3
MEX3D	ENST00000605173.2	c.1276G>A	p.Val426Met	missense_variant	Exon 2 of 3	1		ENSP00000475059.1

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

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

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

Other links and lift over

dbSNP: rs1914515178; hg19: chr19-1555714;