12-120691123-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.236-2968C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 152,082 control chromosomes in the GnomAD database, including 8,963 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.34 (8963 hom., cov: 32)
• Consequence: MLEC NM_014730.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.212

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=-0.86).
• BP6: Variant 12-120691123-C-T is Benign according to our data. Variant chr12-120691123-C-T is described in ClinVar as [Benign]. Clinvar id is 1227142.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MLEC	NM_014730.4	c.236-2968C>T		intron_variant		ENST00000228506.8
MLEC	XM_011539032.2	c.-1708C>T		5_prime_UTR_variant	1/6
MLEC	NM_001303627.2	c.-15+2689C>T		intron_variant
MLEC	NM_001303628.2	c.236-2968C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MLEC	ENST00000228506.8	c.236-2968C>T		intron_variant		1	NM_014730.4	P1
MLEC	ENST00000412616.2	c.236-2968C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51574 AN: 151964 Hom.: 8954 Cov.: 32

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.358

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.359

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.339 AC: 51617 AN: 152082 Hom.: 8963 Cov.: 32 AF XY: 0.343 AC XY: 25517 AN XY: 74336

Gnomad4 AFR AF: 0.368

Gnomad4 AMR AF: 0.377

Gnomad4 ASJ AF: 0.350

Gnomad4 EAS AF: 0.339

Gnomad4 SAS AF: 0.387

Gnomad4 FIN AF: 0.298

Gnomad4 NFE AF: 0.315

Gnomad4 OTH AF: 0.365

Alfa AF: 0.332 Hom.: 8539

Bravo AF: 0.349

Asia WGS AF: 0.376 AC: 1303 AN: 3478

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

Jul 13, 2018

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

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	11
Dann	Benign	0.69

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: rs10431386; hg19: chr12-121128926;