19-1555768-C-G

Variant names:

• chr19-1555768-C-G
• rs751837778
• NM_203304.4:c.1751G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_203304.4(MEX3D):​c.1751G>C​(p.Ser584Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000749 in 1,334,990 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. S584N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: MEX3D NM_203304.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.345
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06368032).

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.1751G>C	p.Ser584Thr	missense	Exon 2 of 2	NP_976049.3	Q86XN8-1
	MEX3D	NM_001174118.2		c.1751G>C	p.Ser584Thr	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.1751G>C	p.Ser584Thr	missense	Exon 2 of 2	ENSP00000384398.3	Q86XN8-1
	MEX3D	ENST00000605173.2	TSL:1	c.1223G>C	p.Ser408Thr	missense	Exon 2 of 3	ENSP00000475059.1	S4R446

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.49e-7 AC: 1 AN: 1334990 Hom.: 0 Cov.: 35 AF XY: 0.00000152 AC XY: 1 AN XY: 656288

African (AFR) AF: 0.00 AC: 0 AN: 27082

American (AMR) AF: 0.00 AC: 0 AN: 29416

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23106

East Asian (EAS) AF: 0.00 AC: 0 AN: 31512

South Asian (SAS) AF: 0.00 AC: 0 AN: 74022

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33226

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4278

European-Non Finnish (NFE) AF: 9.46e-7 AC: 1 AN: 1056912

Other (OTH) AF: 0.00 AC: 0 AN: 55436

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.61
DANN	Benign	0.77
DEOGEN2	Benign	0.013	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.26	T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.064	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.34
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.017
Sift	Benign	0.053	T
Sift4G	Benign	0.25	T
Polyphen		0.12	B
Vest4		0.058
MutPred		0.17		Gain of glycosylation at S581 (P = 0.1128)
MVP		0.099
ClinPred		0.065	T
GERP RS		-4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.038
gMVP		0.31
Mutation Taster		=97/3	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: rs751837778; hg19: chr19-1555767;