chr12-120697664-T-C

Variant names:

• chr12-120697664-T-C
• rs7976497
• NM_014730.4:c.*1119T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_014730.4(MLEC):​c.*1119T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.595 in 152,578 control chromosomes in the GnomAD database, including 29,774 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.60 (29734 hom., cov: 33)
  • Exomes 𝑓: 0.46 (40 hom.)
• Consequence: MLEC NM_014730.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33
• Publications: 22 publications found

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]

ENSG00000256364 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.877 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MLEC	NM_014730.4	c.*1119T>C		3_prime_UTR_variant	Exon 5 of 5	ENST00000228506.8	NP_055545.1
MLEC	NM_001303628.2	c.*1109T>C		3_prime_UTR_variant	Exon 3 of 3		NP_001290557.1
MLEC	NM_001303627.2	c.*1119T>C		3_prime_UTR_variant	Exon 5 of 5		NP_001290556.1
MLEC	XM_011539032.2	c.*1119T>C		3_prime_UTR_variant	Exon 6 of 6		XP_011537334.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MLEC	ENST00000228506.8	c.*1119T>C		3_prime_UTR_variant	Exon 5 of 5	1	NM_014730.4	ENSP00000228506.3
MLEC	ENST00000545525.6	c.*1119T>C		3_prime_UTR_variant	Exon 4 of 4	2		ENSP00000438950.2
MLEC	ENST00000535413.1	n.139+1123T>C		intron_variant	Intron 1 of 1	2
ENSG00000256364	ENST00000541383.1	n.252-217A>G		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.595 AC: 90507 AN: 152026 Hom.: 29679 Cov.: 33

Gnomad AFR AF: 0.884

Gnomad AMI AF: 0.440

Gnomad AMR AF: 0.596

Gnomad ASJ AF: 0.509

Gnomad EAS AF: 0.533

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.586

GnomAD4 exome AF: 0.459 AC: 199 AN: 434 Hom.: 40 Cov.: 0 AF XY: 0.492 AC XY: 126 AN XY: 256

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.457 AC: 189 AN: 414

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 8 AN: 16

Other (OTH) AF: 0.500 AC: 2 AN: 4

GnomAD4 genome AF: 0.596 AC: 90615 AN: 152144 Hom.: 29734 Cov.: 33 AF XY: 0.601 AC XY: 44709 AN XY: 74388

African (AFR) AF: 0.884 AC: 36748 AN: 41552

American (AMR) AF: 0.595 AC: 9100 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.509 AC: 1766 AN: 3468

East Asian (EAS) AF: 0.532 AC: 2754 AN: 5172

South Asian (SAS) AF: 0.646 AC: 3116 AN: 4824

European-Finnish (FIN) AF: 0.462 AC: 4880 AN: 10562

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.448 AC: 30424 AN: 67958

Other (OTH) AF: 0.589 AC: 1247 AN: 2116

Alfa AF: 0.501 Hom.: 83316

Bravo AF: 0.617

Asia WGS AF: 0.629 AC: 2185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	16
DANN	Benign	0.90
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7976497; hg19: chr12-121135467; COSMIC: COSV57329971; COSMIC: COSV57329971;