19-1555948-C-A

Variant names:

• chr19-1555948-C-A
• rs1230314184
• NM_203304.4:c.1571G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_203304.4(MEX3D):​c.1571G>T​(p.Arg524Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000111 in 1,171,640 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R524C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000034 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000078 (0 hom.)
• Consequence: MEX3D NM_203304.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.00600
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.059115708).

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.1571G>T	p.Arg524Leu	missense	Exon 2 of 2	NP_976049.3	Q86XN8-1
	MEX3D	NM_001174118.2		c.1571G>T	p.Arg524Leu	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.1571G>T	p.Arg524Leu	missense	Exon 2 of 2	ENSP00000384398.3	Q86XN8-1
	MEX3D	ENST00000605173.2	TSL:1	c.1043G>T	p.Arg348Leu	missense	Exon 2 of 3	ENSP00000475059.1	S4R446

Frequencies

GnomAD3 genomes AF: 0.0000336 AC: 5 AN: 148844 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000974

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000782 AC: 8 AN: 1022688 Hom.: 0 Cov.: 34 AF XY: 0.00000207 AC XY: 1 AN XY: 483254

African (AFR) AF: 0.00 AC: 0 AN: 19744

American (AMR) AF: 0.00 AC: 0 AN: 5948

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10988

East Asian (EAS) AF: 0.000371 AC: 7 AN: 18860

South Asian (SAS) AF: 0.00 AC: 0 AN: 22788

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20120

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2530

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 882868

Other (OTH) AF: 0.0000257 AC: 1 AN: 38842

GnomAD4 genome AF: 0.0000336 AC: 5 AN: 148952 Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 1 AN XY: 72702

African (AFR) AF: 0.00 AC: 0 AN: 41192

American (AMR) AF: 0.00 AC: 0 AN: 15004

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3418

East Asian (EAS) AF: 0.000977 AC: 5 AN: 5120

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9346

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66788

Other (OTH) AF: 0.00 AC: 0 AN: 2072

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

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	Benign	0.074
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	13
DANN	Benign	0.96
DEOGEN2	Benign	0.0042	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.54	T
M_CAP	Uncertain	0.089	D
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.76	N
PhyloP100		-0.0060
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.25	N
REVEL	Benign	0.045
Sift	Benign	0.21	T
Sift4G	Benign	0.26	T
Polyphen		0.0	B
Vest4		0.17
MutPred		0.34		Loss of methylation at R524 (P = 0.0261)
MVP		0.18
ClinPred		0.12	T
GERP RS		-0.040
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
Varity_R		0.065
gMVP		0.45
Mutation Taster		=99/1	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: rs1230314184; hg19: chr19-1555947;