chr12-120696516-C-T

Position:

• chr12-120696516-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_014730.4(MLEC):​c.850C>T​(p.Pro284Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MLEC NM_014730.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.51

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.856

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MLEC	NM_014730.4	c.850C>T	p.Pro284Ser	missense_variant	5/5	ENST00000228506.8	NP_055545.1
MLEC	NM_001303627.2	c.601C>T	p.Pro201Ser	missense_variant	5/5		NP_001290556.1
MLEC	XM_011539032.2	c.601C>T	p.Pro201Ser	missense_variant	6/6		XP_011537334.1
MLEC	NM_001303628.2	c.615C>T	p.Phe205Phe	synonymous_variant	3/3		NP_001290557.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MLEC	ENST00000228506.8	c.850C>T	p.Pro284Ser	missense_variant	5/5	1	NM_014730.4	ENSP00000228506.3
MLEC	ENST00000412616.2	c.615C>T	p.Phe205Phe	synonymous_variant	3/3	3		ENSP00000440746.1
MLEC	ENST00000535656.1	c.480C>T	p.Phe160Phe	synonymous_variant	3/3	3		ENSP00000441247.1
MLEC	ENST00000535413.1	n.114C>T		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 21, 2024

The c.850C>T (p.P284S) alteration is located in exon 5 (coding exon 5) of the MLEC gene. This alteration results from a C to T substitution at nucleotide position 850, causing the proline (P) at amino acid position 284 to be replaced by a serine (S). 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	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.44	T
Eigen	Pathogenic	0.88
Eigen_PC	Pathogenic	0.85
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Benign	0.017	T
MetaRNN	Pathogenic	0.86	D
MetaSVM	Uncertain	0.12	D
MutationAssessor	Benign	2.0	M
PrimateAI	Pathogenic	0.91	D
PROVEAN	Pathogenic	-7.2	D
REVEL	Pathogenic	0.74
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.013	D
Polyphen		1.0	D
Vest4		0.69
MutPred		0.76		Gain of glycosylation at P284 (P = 0.0365);
MVP		0.54
MPC		2.2
ClinPred		0.99	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.67
gMVP		0.95

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-121134319;