Variant chr12-120687412-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014730.4(MLEC):c.116C>T(p.Ala39Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000129 in 1,388,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

MLEC
NM_014730.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.187

Variant links:

Genes affected

MLEC (HGNC:28973): (malectin) This gene encodes the carbohydrate-binding protein malectin which is a Type I membrane-anchored endoplasmic reticulum protein. This protein has an affinity for Glc2Man9GlcNAc2 (G2M9) N-glycans and is involved in regulating glycosylation in the endoplasmic reticulum. This protein has also been shown to interact with ribophorin I and may be involved in the directing the degradation of misfolded proteins. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

MLEC links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.045808077).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MLEC	NM_014730.4 linkuse as main transcript	c.116C>T	p.Ala39Val	missense_variant	1/5	ENST00000228506.8	NP_055545.1	Q14165
MLEC	NM_001303628.2 linkuse as main transcript	c.116C>T	p.Ala39Val	missense_variant	1/3		NP_001290557.1	F5GX14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MLEC	ENST00000228506.8 linkuse as main transcript	c.116C>T	p.Ala39Val	missense_variant	1/5	1	NM_014730.4	ENSP00000228506.3		Q14165
MLEC	ENST00000412616.2 linkuse as main transcript	c.116C>T	p.Ala39Val	missense_variant	1/3	3		ENSP00000440746.1		F5GX14

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

151944

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

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:

0.000191

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000523

AC:

AN:

95570

Hom.:

AF XY:

0.0000370

AC XY:

AN XY:

54114

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000101

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000130

AC:

161

AN:

1236892

Hom.:

Cov.:

AF XY:

0.000129

AC XY:

AN XY:

602906

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000607

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000222

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000150

Gnomad4 OTH exome

AF:

0.000100

GnomAD4 genome

AF:

0.000118

AC:

AN:

151944

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74196

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000285

Hom.:

Bravo

AF:

0.000140

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000127

AC:

ExAC

AF:

0.0000444

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 08, 2024

The c.116C>T (p.A39V) alteration is located in exon 1 (coding exon 1) of the MLEC gene. This alteration results from a C to T substitution at nucleotide position 116, causing the alanine (A) at amino acid position 39 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.026

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.53

T;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.046

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

N;.

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.70

N;N

REVEL

Benign

0.043

Sift

Benign

0.15

T;D

Sift4G

Benign

0.45

T;D

Polyphen

0.0

B;.

Vest4

0.073

MVP

0.14

MPC

0.97

ClinPred

0.050

GERP RS

-1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

Varity_R

0.043

gMVP

0.30

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over