chr19-1555360-C-G

Variant names:

• chr19-1555360-C-G
• rs376659727
• ENST00000605173.2:c.1444G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001174118.2(MEX3D):​c.1972G>C​(p.Gly658Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 10/11 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. G658S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: MEX3D NM_001174118.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10932112).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEX3D	NM_203304.4	c.*203G>C		3_prime_UTR_variant	Exon 2 of 2	ENST00000402693.5	NP_976049.3
MEX3D	NM_001174118.2	c.1972G>C	p.Gly658Arg	missense_variant	Exon 3 of 3		NP_001167589.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEX3D	ENST00000605173.2	c.1444G>C	p.Gly482Arg	missense_variant	Exon 3 of 3	1		ENSP00000475059.1
MEX3D	ENST00000402693	c.*203G>C		3_prime_UTR_variant	Exon 2 of 2	1	NM_203304.4	ENSP00000384398.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.29
DANN	Benign	0.94
DEOGEN2	Benign	0.0053	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.099	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.055	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.90	T
Sift4G	Pathogenic	0.0	D
MVP		0.081
ClinPred		0.061	T
GERP RS		-8.7

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: rs376659727; hg19: chr19-1555359;