chr19-1555927-C-G

Variant names:

• chr19-1555927-C-G
• NM_203304.4:c.1592G>C

Variant summary

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

The NM_203304.4(MEX3D):​c.1592G>C​(p.Arg531Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MEX3D NM_203304.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.34

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.1592G>C	p.Arg531Pro	missense_variant	Exon 2 of 2	ENST00000402693.5	NP_976049.3
MEX3D	NM_001174118.2	c.1592G>C	p.Arg531Pro	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.1592G>C	p.Arg531Pro	missense_variant	Exon 2 of 2	1	NM_203304.4	ENSP00000384398.3
MEX3D	ENST00000605173.2	c.1064G>C	p.Arg355Pro	missense_variant	Exon 2 of 3	1		ENSP00000475059.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 31, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1592G>C (p.R531P) alteration is located in exon 2 (coding exon 2) of the MEX3D gene. This alteration results from a G to C substitution at nucleotide position 1592, causing the arginine (R) at amino acid position 531 to be replaced by a proline (P). 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	Benign	0.11
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T;T
Eigen	Uncertain	0.33
Eigen_PC	Benign	0.21
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.56	T;T
M_CAP	Pathogenic	0.72	D
MetaRNN	Uncertain	0.61	D;D
MetaSVM	Benign	-0.49	T
MutationAssessor	Uncertain	2.3	M;.
PrimateAI	Pathogenic	0.91	D
PROVEAN	Uncertain	-3.2	D;.
REVEL	Benign	0.24
Sift	Uncertain	0.0010	D;.
Sift4G	Uncertain	0.054	T;T
Polyphen		1.0	D;.
Vest4		0.53
MutPred		0.34		Gain of sheet (P = 0.0061);.;
MVP		0.52
ClinPred		0.99	D
GERP RS		4.0
Varity_R		0.72
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-1555926;