rs769841602

Variant names:

• chr15-82043803-C-A
• rs769841602
• NM_032246.6:c.1067G>T

Your query was ambiguous. Multiple possible variants found:

• chr15-82043803-C-A
• chr15-82043803-C-T

Variant summary

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

The NM_032246.6(MEX3B):​c.1067G>T​(p.Cys356Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000279 in 1,432,854 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. C356Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: MEX3B NM_032246.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.307
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1289112).

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.1067G>T	p.Cys356Phe	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.1067G>T	p.Cys356Phe	missense	Exon 2 of 2	ENSP00000329918.4	Q6ZN04-1
	MEX3B	ENST00000558133.1	TSL:6	c.*1426G>T		3_prime_UTR	Exon 1 of 1	ENSP00000456938.1	Q6ZN04-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000894 AC: 2 AN: 223728 AF XY: 0.0000166

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000279 AC: 4 AN: 1432854 Hom.: 0 Cov.: 33 AF XY: 0.00000282 AC XY: 2 AN XY: 710180

African (AFR) AF: 0.00 AC: 0 AN: 32578

American (AMR) AF: 0.00 AC: 0 AN: 40684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23922

East Asian (EAS) AF: 0.00 AC: 0 AN: 39516

South Asian (SAS) AF: 0.0000494 AC: 4 AN: 81036

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51982

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5606

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1098420

Other (OTH) AF: 0.00 AC: 0 AN: 59110

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	22
DANN	Benign	0.95
DEOGEN2	Benign	0.057	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.50	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.066	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.31
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.11
Sift	Benign	0.22	T
Sift4G	Benign	0.49	T
Polyphen		0.64	P
Vest4		0.25
MutPred		0.18		Loss of helix (P = 0.0821)
MVP		0.30
MPC		1.0
ClinPred		0.36	T
GERP RS		3.8
Varity_R		0.17
gMVP		0.48
Mutation Taster		=86/14	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: rs769841602; hg19: chr15-82336144;