12-120694297-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014730.4(MLEC):c.414+28C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 1,606,068 control chromosomes in the GnomAD database, including 129,963 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.49 (20983 hom., cov: 32)
  • Exomes 𝑓: 0.38 (108980 hom.)
• Consequence: MLEC NM_014730.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.107

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 12-120694297-C-T is Benign according to our data. Variant chr12-120694297-C-T is described in ClinVar as [Benign]. Clinvar id is 1237132.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.774 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MLEC	NM_014730.4	c.414+28C>T		intron_variant		ENST00000228506.8
MLEC	NM_001303627.2	c.165+28C>T		intron_variant
MLEC	NM_001303628.2	c.414+28C>T		intron_variant
MLEC	XM_011539032.2	c.165+28C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MLEC	ENST00000228506.8	c.414+28C>T		intron_variant		1	NM_014730.4	P1
MLEC	ENST00000412616.2	c.414+28C>T		intron_variant		3
MLEC	ENST00000535656.1	c.103+28C>T		intron_variant		3
MLEC	ENST00000545525.5	c.165+28C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.490 AC: 74495 AN: 151904 Hom.: 20939 Cov.: 32

Gnomad AFR AF: 0.781

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.472

GnomAD3 exomes AF: 0.434 AC: 107215 AN: 246814 Hom.: 24990 AF XY: 0.425 AC XY: 56671 AN XY: 133334

Gnomad AFR exome AF: 0.787

Gnomad AMR exome AF: 0.522

Gnomad ASJ exome AF: 0.410

Gnomad EAS exome AF: 0.482

Gnomad SAS exome AF: 0.478

Gnomad FIN exome AF: 0.339

Gnomad NFE exome AF: 0.357

Gnomad OTH exome AF: 0.429

GnomAD4 exome AF: 0.378 AC: 548989 AN: 1454046 Hom.: 108980 Cov.: 31 AF XY: 0.379 AC XY: 274269 AN XY: 723040

Gnomad4 AFR exome AF: 0.798

Gnomad4 AMR exome AF: 0.515

Gnomad4 ASJ exome AF: 0.414

Gnomad4 EAS exome AF: 0.427

Gnomad4 SAS exome AF: 0.478

Gnomad4 FIN exome AF: 0.335

Gnomad4 NFE exome AF: 0.348

Gnomad4 OTH exome AF: 0.417

GnomAD4 genome AF: 0.491 AC: 74596 AN: 152022 Hom.: 20983 Cov.: 32 AF XY: 0.493 AC XY: 36604 AN XY: 74320

Gnomad4 AFR AF: 0.781

Gnomad4 AMR AF: 0.465

Gnomad4 ASJ AF: 0.406

Gnomad4 EAS AF: 0.486

Gnomad4 SAS AF: 0.471

Gnomad4 FIN AF: 0.331

Gnomad4 NFE AF: 0.352

Gnomad4 OTH AF: 0.477

Alfa AF: 0.401 Hom.: 14321

Bravo AF: 0.515

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 10, 2019

This variant is associated with the following publications: (PMID: 28972276) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
Cadd	Benign	9.7
Dann	Benign	0.67
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs7964786; hg19: chr12-121132100; COSMIC: COSV57330667; COSMIC: COSV57330667;