rs1914515178

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203304.4. 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
	MEX3D	NM_203304.4	MANE Select	c.1804G>A	p.Val602Met	missense	Exon 2 of 2	NP_976049.3	Q86XN8-1
	MEX3D	NM_001174118.2		c.1804G>A	p.Val602Met	missense	Exon 2 of 3	NP_001167589.1	Q86XN8-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEX3D	ENST00000402693.5	TSL:1 MANE Select	c.1804G>A	p.Val602Met	missense	Exon 2 of 2	ENSP00000384398.3	Q86XN8-1
	MEX3D	ENST00000605173.2	TSL:1	c.1276G>A	p.Val426Met	missense	Exon 2 of 3	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

African (AFR) AF: 0.0000329 AC: 1 AN: 30378

American (AMR) AF: 0.00 AC: 0 AN: 36426

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25020

East Asian (EAS) AF: 0.00 AC: 0 AN: 35216

South Asian (SAS) AF: 0.00 AC: 0 AN: 79144

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38964

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5326

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1082704

Other (OTH) AF: 0.00 AC: 0 AN: 58038

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Benign	0.67	D
LIST_S2	Uncertain	0.87	D
M_CAP	Pathogenic	0.86	D
MetaRNN	Uncertain	0.71	D
MetaSVM	Uncertain	-0.16	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		1.8
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.53
Sift	Uncertain	0.011	D
Sift4G	Benign	0.089	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
Mutation Taster		=65/35	polymorphism

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

Other links and lift over

dbSNP: rs1914515178; hg19: chr19-1555714;