rs369746192

Variant names:

• chr15-82043557-C-A
• rs369746192
• NM_032246.6:c.1313G>T

Your query was ambiguous. Multiple possible variants found:

• chr15-82043557-C-A
• chr15-82043557-C-G
• chr15-82043557-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032246.6(MEX3B):​c.1313G>T​(p.Cys438Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000072 in 1,388,214 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. 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. C438Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: MEX3B NM_032246.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.11
• Publications: 0 publications found

Genes affected

MEX3B (HGNC:25297): (mex-3 RNA binding family member B) This gene encodes an RNA-binding phosphoprotein that is part of the MEX3 (muscle excess 3) family of translational regulators. The encoded protein contains N-terminal nuclear export and nuclear localization signals and is exported from the cytoplasm to the nucleus. The protein binds to RNA via two KH domains and also colocalizes with MEX3A, Dcp1A decapping factor and Argonaute proteins within P (processing) bodies. [provided by RefSeq, Oct 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38815704).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032246.6. 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
	MEX3B	NM_032246.6	MANE Select	c.1313G>T	p.Cys438Phe	missense	Exon 2 of 2	NP_115622.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEX3B	ENST00000329713.5	TSL:1 MANE Select	c.1313G>T	p.Cys438Phe	missense	Exon 2 of 2	ENSP00000329918.4	Q6ZN04-1
	MEX3B	ENST00000558133.1	TSL:6	c.*1672G>T		3_prime_UTR	Exon 1 of 1	ENSP00000456938.1	Q6ZN04-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.20e-7 AC: 1 AN: 1388214 Hom.: 0 Cov.: 33 AF XY: 0.00000146 AC XY: 1 AN XY: 685246

African (AFR) AF: 0.00 AC: 0 AN: 31070

American (AMR) AF: 0.00 AC: 0 AN: 31706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22630

East Asian (EAS) AF: 0.00 AC: 0 AN: 37006

South Asian (SAS) AF: 0.00 AC: 0 AN: 75802

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48984

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5518

European-Non Finnish (NFE) AF: 9.28e-7 AC: 1 AN: 1078100

Other (OTH) AF: 0.00 AC: 0 AN: 57398

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.083	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.032	T
Eigen	Benign	0.083
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.072	D
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PhyloP100		2.1
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.11
Sift	Uncertain	0.014	D
Sift4G	Benign	0.26	T
Polyphen		0.80	P
Vest4		0.64
MutPred		0.15		Gain of glycosylation at T436 (P = 0.0701)
MVP		0.48
MPC		1.1
ClinPred		0.39	T
GERP RS		4.7
Varity_R		0.51
gMVP		0.34
Mutation Taster		=83/17	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: rs369746192; hg19: chr15-82335898;