Variant chr12-120696316-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014730.4(MLEC):c.650A>G(p.Asp217Gly) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,740 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

MLEC
NM_014730.4 missense, splice_region

Scores

Splicing: ADA: 0.0001529

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.88

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MLEC	NM_014730.4 linkuse as main transcript	c.650A>G	p.Asp217Gly	missense_variant, splice_region_variant	5/5	ENST00000228506.8	NP_055545.1	Q14165
MLEC	NM_001303628.2 linkuse as main transcript	c.415A>G	p.Met139Val	missense_variant, splice_region_variant	3/3		NP_001290557.1	F5GX14
MLEC	NM_001303627.2 linkuse as main transcript	c.401A>G	p.Asp134Gly	missense_variant, splice_region_variant	5/5		NP_001290556.1
MLEC	XM_011539032.2 linkuse as main transcript	c.401A>G	p.Asp134Gly	missense_variant, splice_region_variant	6/6		XP_011537334.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MLEC	ENST00000228506.8 linkuse as main transcript	c.650A>G	p.Asp217Gly	missense_variant, splice_region_variant	5/5	1	NM_014730.4	ENSP00000228506.3	Q14165
MLEC	ENST00000412616.2 linkuse as main transcript	c.415A>G	p.Met139Val	missense_variant, splice_region_variant	3/3	3		ENSP00000440746.1	F5GX14
MLEC	ENST00000535656.1 linkuse as main transcript	c.280A>G	p.Met94Val	missense_variant, splice_region_variant	3/3	3		ENSP00000441247.1	H0YG07
MLEC	ENST00000545525.5 linkuse as main transcript	c.401A>G	p.Asp134Gly	missense_variant, splice_region_variant	4/4	2		ENSP00000438950.2	F5H1S8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251156

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135778

show subpopulations

Gnomad AFR exome

AF:

0.0000618

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461740

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

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

Jul 30, 2024

The c.650A>G (p.D217G) alteration is located in exon 5 (coding exon 5) of the MLEC gene. This alteration results from a A to G substitution at nucleotide position 650, causing the aspartic acid (D) at amino acid position 217 to be replaced by a glycine (G). 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

Uncertain

0.35

BayesDel_addAF

Benign

-0.023

BayesDel_noAF

Benign

-0.090

CADD

Uncertain

DANN

Benign

0.74

DEOGEN2

Benign

0.27

T;T

Eigen

Pathogenic

0.72

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

D;D

M_CAP

Uncertain

0.094

MetaRNN

Uncertain

0.56

D;D

MetaSVM

Benign

-0.73

MutationAssessor

Benign

1.8

L;.

PrimateAI

Uncertain

0.65

PROVEAN

Pathogenic

-5.4

D;D

REVEL

Uncertain

0.41

Sift

Uncertain

0.0040

D;D

Sift4G

Uncertain

0.010

D;D

Polyphen

0.99

D;.

Vest4

0.36

MutPred

0.32

Gain of catalytic residue at V218 (P = 0.0912);.;

MVP

0.54

MPC

2.3

ClinPred

0.92

GERP RS

5.1

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Varity_R

0.75

gMVP

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00015

dbscSNV1_RF

Benign

0.028

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