rs7976497

Positions:

• chr12-120697664-T-C
• chr12-120697664-T-G

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
MLEC	NM_014730.4	c.*1119T>C		3_prime_UTR_variant	5/5	ENST00000228506.8	NP_055545.1
MLEC	NM_001303627.2	c.*1119T>C		3_prime_UTR_variant	5/5		NP_001290556.1
MLEC	NM_001303628.2	c.*1109T>C		3_prime_UTR_variant	3/3		NP_001290557.1
MLEC	XM_011539032.2	c.*1119T>C		3_prime_UTR_variant	6/6		XP_011537334.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MLEC	ENST00000228506.8	c.*1119T>C		3_prime_UTR_variant	5/5	1	NM_014730.4	ENSP00000228506	P1
	ENST00000541383.1	n.252-217A>G		intron_variant, non_coding_transcript_variant		3
MLEC	ENST00000535413.1	n.139+1123T>C		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 FIN exome AF: 0.457

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.500

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

Gnomad4 AFR AF: 0.884

Gnomad4 AMR AF: 0.595

Gnomad4 ASJ AF: 0.509

Gnomad4 EAS AF: 0.532

Gnomad4 SAS AF: 0.646

Gnomad4 FIN AF: 0.462

Gnomad4 NFE AF: 0.448

Gnomad4 OTH AF: 0.589

Alfa AF: 0.486 Hom.: 37394

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

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