19-1555948-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_203304.4(MEX3D):​c.1571G>C​(p.Arg524Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000978 in 1,022,688 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R524L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 9.8e-7 (0 hom.)
• Consequence: MEX3D NM_203304.4 missense
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.073556185).

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>C	p.Arg524Pro	missense	Exon 2 of 2	NP_976049.3	Q86XN8-1
	MEX3D	NM_001174118.2		c.1571G>C	p.Arg524Pro	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>C	p.Arg524Pro	missense	Exon 2 of 2	ENSP00000384398.3	Q86XN8-1
	MEX3D	ENST00000605173.2	TSL:1	c.1043G>C	p.Arg348Pro	missense	Exon 2 of 3	ENSP00000475059.1	S4R446

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.78e-7 AC: 1 AN: 1022688 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 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: 0.00 AC: 0 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: 0.00000113 AC: 1 AN: 882868

Other (OTH) AF: 0.00 AC: 0 AN: 38842

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	13
DANN	Benign	0.94
DEOGEN2	Benign	0.0015	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.085	D
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.18	N
PhyloP100		-0.0060
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	1.4	N
REVEL	Benign	0.054
Sift	Benign	0.21	T
Sift4G	Benign	0.49	T
Polyphen		0.16	B
Vest4		0.17
MutPred		0.24		Loss of methylation at R524 (P = 0.0261)
MVP		0.19
ClinPred		0.23	T
GERP RS		-0.040
Varity_R		0.18
gMVP		0.49
Mutation Taster		=82/18	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;