12-120696471-A-G

Position:

• chr12-120696471-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014730.4(MLEC):​c.805A>G​(p.Ser269Gly) 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 benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MLEC NM_014730.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.88

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35327935).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MLEC	NM_014730.4	c.805A>G	p.Ser269Gly	missense_variant	5/5	ENST00000228506.8	NP_055545.1
MLEC	NM_001303627.2	c.556A>G	p.Ser186Gly	missense_variant	5/5		NP_001290556.1
MLEC	XM_011539032.2	c.556A>G	p.Ser186Gly	missense_variant	6/6		XP_011537334.1
MLEC	NM_001303628.2	c.570A>G	p.Thr190=	synonymous_variant	3/3		NP_001290557.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MLEC	ENST00000228506.8	c.805A>G	p.Ser269Gly	missense_variant	5/5	1	NM_014730.4	ENSP00000228506	P1
MLEC	ENST00000412616.2	c.570A>G	p.Thr190=	synonymous_variant	3/3	3		ENSP00000440746
MLEC	ENST00000535656.1	c.438A>G	p.Thr146=	synonymous_variant	3/3	3		ENSP00000441247
MLEC	ENST00000535413.1	n.69A>G		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

Mar 28, 2023

The c.805A>G (p.S269G) 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 805, causing the serine (S) at amino acid position 269 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	Pathogenic	0.62
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	1.5	L
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.51
Sift	Benign	0.031	D
Sift4G	Benign	0.12	T
Polyphen		0.65	P
Vest4		0.52
MutPred		0.51		Gain of relative solvent accessibility (P = 0.0249);
MVP		0.55
MPC		1.1
ClinPred		0.92	D
GERP RS		5.4
Varity_R		0.44
gMVP		0.81

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: chr12-121134274;