chr19-1555360-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001174118.2(MEX3D):​c.1972G>A​(p.Gly658Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000139 in 1,601,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00017 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00014 (0 hom.)
• Consequence: MEX3D NM_001174118.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.09
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.035033137).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001174118.2. 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.*203G>A		3_prime_UTR	Exon 2 of 2	NP_976049.3	Q86XN8-1
	MEX3D	NM_001174118.2		c.1972G>A	p.Gly658Ser	missense	Exon 3 of 3	NP_001167589.1	Q86XN8-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEX3D	ENST00000605173.2	TSL:1	c.1444G>A	p.Gly482Ser	missense	Exon 3 of 3	ENSP00000475059.1	S4R446
	MEX3D	ENST00000402693.5	TSL:1 MANE Select	c.*203G>A		3_prime_UTR	Exon 2 of 2	ENSP00000384398.3	Q86XN8-1

Frequencies

GnomAD3 genomes AF: 0.000171 AC: 26 AN: 152008 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000133 AC: 33 AN: 248816 AF XY: 0.000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000277

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.000136 AC: 197 AN: 1449754 Hom.: 0 Cov.: 31 AF XY: 0.000119 AC XY: 86 AN XY: 721492

African (AFR) AF: 0.00 AC: 0 AN: 33038

American (AMR) AF: 0.0000676 AC: 3 AN: 44400

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25688

East Asian (EAS) AF: 0.00 AC: 0 AN: 37954

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85286

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51992

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5720

European-Non Finnish (NFE) AF: 0.000173 AC: 191 AN: 1106094

Other (OTH) AF: 0.0000336 AC: 2 AN: 59582

GnomAD4 genome AF: 0.000171 AC: 26 AN: 152122 Hom.: 0 Cov.: 31 AF XY: 0.000161 AC XY: 12 AN XY: 74368

African (AFR) AF: 0.0000241 AC: 1 AN: 41550

American (AMR) AF: 0.000131 AC: 2 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5070

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000338 AC: 23 AN: 68000

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000164 Hom.: 0

Bravo AF: 0.000132

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000174 AC: 21

EpiCase AF: 0.000273

EpiControl AF: 0.000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.53
DANN	Benign	0.90
DEOGEN2	Benign	0.0032	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.059	D
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-0.90	T
PhyloP100		-1.1
Sift4G	Pathogenic	0.0	D
MVP		0.014
ClinPred		0.031	T
GERP RS		-8.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=99/1	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: rs376659727; hg19: chr19-1555359;