rs1285933

Variant names:

• chr7-141927349-G-A
• rs1285933
• ENST00000465654.5:c.-179-18472G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000465654.5(MGAM):​c.-179-18472G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 152,056 control chromosomes in the GnomAD database, including 21,650 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 0.53 (21648 hom., cov: 32)
  • Exomes 𝑓: 0.43 (2 hom.)
• Consequence: MGAM ENST00000465654.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0260
• Publications: 32 publications found

Genes affected

MGAM (HGNC:7043): (maltase-glucoamylase) This gene encodes maltase-glucoamylase, which is a brush border membrane enzyme that plays a role in the final steps of digestion of starch. The protein has two catalytic sites identical to those of sucrase-isomaltase, but the proteins are only 59% homologous. Both are members of glycosyl hydrolase family 31, which has a variety of substrate specificities. [provided by RefSeq, Jul 2008]

CLEC5A (HGNC:2054): (C-type lectin domain containing 5A) This gene encodes a member of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily. Members of this family share a common protein fold and have diverse functions, such as cell adhesion, cell-cell signalling, glycoprotein turnover, and roles in inflammation and immune response. The encoded type II transmembrane protein interacts with dnax-activation protein 12 and may play a role in cell activation. Alternative splice variants have been described but their full-length sequence has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000465654.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC5A	NM_013252.3	MANE Select	c.*2755C>T		downstream_gene	N/A	NP_037384.1	Q9NY25-1
	CLEC5A	NM_001301167.2		c.*2755C>T		downstream_gene	N/A	NP_001288096.1	Q14DL9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGAM	ENST00000465654.5	TSL:3	c.-179-18472G>A		intron	N/A	ENSP00000419372.1	E7EW87
	MGAM	ENST00000497554.1	TSL:3	n.37-2428G>A		intron	N/A
	CLEC5A	ENST00000546910.6	TSL:1 MANE Select	c.*2755C>T		downstream_gene	N/A	ENSP00000449999.1	Q9NY25-1

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80396 AN: 151924 Hom.: 21637 Cov.: 32

Gnomad AFR AF: 0.613

Gnomad AMI AF: 0.746

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.521

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.522

Gnomad OTH AF: 0.519

GnomAD4 exome AF: 0.429 AC: 6 AN: 14 Hom.: 2 Cov.: 0 AF XY: 0.429 AC XY: 6 AN XY: 14

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: 1.00 AC: 2 AN: 2

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.167 AC: 1 AN: 6

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

GnomAD4 genome AF: 0.529 AC: 80439 AN: 152042 Hom.: 21648 Cov.: 32 AF XY: 0.523 AC XY: 38877 AN XY: 74328

African (AFR) AF: 0.612 AC: 25392 AN: 41466

American (AMR) AF: 0.465 AC: 7107 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.551 AC: 1910 AN: 3468

East Asian (EAS) AF: 0.217 AC: 1121 AN: 5162

South Asian (SAS) AF: 0.416 AC: 2007 AN: 4822

European-Finnish (FIN) AF: 0.521 AC: 5502 AN: 10562

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.522 AC: 35487 AN: 67960

Other (OTH) AF: 0.514 AC: 1085 AN: 2110

Alfa AF: 0.523 Hom.: 35561

Bravo AF: 0.525

Asia WGS AF: 0.315 AC: 1096 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.82
DANN	Benign	0.65
PhyloP100		-0.026
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1285933; hg19: chr7-141627149; COSMIC: COSV107521610;