Variant 12-120696377-A-C 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.711A>C(p.Glu237Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000224 in 1,614,220 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00023 ( 1 hom. )

Consequence

MLEC
NM_014730.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.597

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:

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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=0.016650885).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MLEC	NM_014730.4 linkuse as main transcript	c.711A>C	p.Glu237Asp	missense_variant	5/5	ENST00000228506.8
MLEC	NM_001303628.2 linkuse as main transcript	c.476A>C	p.Lys159Thr	missense_variant	3/3
MLEC	NM_001303627.2 linkuse as main transcript	c.462A>C	p.Glu154Asp	missense_variant	5/5
MLEC	XM_011539032.2 linkuse as main transcript	c.462A>C	p.Glu154Asp	missense_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MLEC	ENST00000228506.8 linkuse as main transcript	c.711A>C	p.Glu237Asp	missense_variant	5/5	1	NM_014730.4	P1

Frequencies

GnomAD3 genomes

AF:

0.000204

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000411

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000211

AC:

AN:

251418

Hom.:

AF XY:

0.000206

AC XY:

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000369

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000226

AC:

330

AN:

1461888

Hom.:

Cov.:

AF XY:

0.000230

AC XY:

167

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000255

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000255

Gnomad4 OTH exome

AF:

0.000298

GnomAD4 genome

AF:

0.000204

AC:

AN:

152332

Hom.:

Cov.:

AF XY:

0.000201

AC XY:

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000412

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000300

Hom.:

Bravo

AF:

0.000159

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.000181

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

Apr 07, 2022

The c.711A>C (p.E237D) alteration is located in exon 5 (coding exon 5) of the MLEC gene. This alteration results from a A to C substitution at nucleotide position 711, causing the glutamic acid (E) at amino acid position 237 to be replaced by an aspartic acid (D). 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

0.069

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

Cadd

Benign

Dann

Benign

0.92

DEOGEN2

Benign

0.025

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.13

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.78

M_CAP

Benign

0.0031

MetaRNN

Benign

0.017

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.28

MutationTaster

Benign

1.0

D;N

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.54

REVEL

Benign

0.085

Sift

Benign

0.58

Sift4G

Benign

0.63

Polyphen

0.0

Vest4

0.079

MutPred

0.12

Loss of helix (P = 0.1299);

MVP

0.14

MPC

0.89

ClinPred

0.011

GERP RS

1.2

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

3.9

Varity_R

0.032

gMVP

0.42

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