7-141947222-A-G

Variant names:

• chr7-141947222-A-G
• rs1285968
• ENST00000465654.5:c.-3+1225A>G

Variant summary

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

The ENST00000465654.5(MGAM):​c.-3+1225A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 152,098 control chromosomes in the GnomAD database, including 32,936 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 0.66 (32936 hom., cov: 33)
• Consequence: MGAM ENST00000465654.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.331
• Publications: 6 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.684 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.-436T>C		upstream_gene	N/A	NP_037384.1	Q9NY25-1
	CLEC5A	NM_001301167.2		c.-436T>C		upstream_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.-3+1225A>G		intron	N/A	ENSP00000419372.1	E7EW87
	CLEC5A	ENST00000546910.6	TSL:1 MANE Select	c.-436T>C		upstream_gene	N/A	ENSP00000449999.1	Q9NY25-1
	CLEC5A	ENST00000418498.5	TSL:1	n.-436T>C		upstream_gene	N/A	ENSP00000392561.1	F8WCL0

Frequencies

GnomAD3 genomes AF: 0.656 AC: 99665 AN: 151980 Hom.: 32928 Cov.: 33

Gnomad AFR AF: 0.641

Gnomad AMI AF: 0.849

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.674

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.677

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.689

Gnomad OTH AF: 0.656

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

GnomAD4 genome AF: 0.656 AC: 99709 AN: 152098 Hom.: 32936 Cov.: 33 AF XY: 0.651 AC XY: 48411 AN XY: 74340

African (AFR) AF: 0.641 AC: 26567 AN: 41476

American (AMR) AF: 0.598 AC: 9129 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.674 AC: 2337 AN: 3466

East Asian (EAS) AF: 0.478 AC: 2477 AN: 5178

South Asian (SAS) AF: 0.584 AC: 2816 AN: 4822

European-Finnish (FIN) AF: 0.677 AC: 7165 AN: 10582

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.689 AC: 46868 AN: 67998

Other (OTH) AF: 0.653 AC: 1380 AN: 2112

Alfa AF: 0.657 Hom.: 10900

Bravo AF: 0.646

Asia WGS AF: 0.517 AC: 1798 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.0
DANN	Benign	0.72
PhyloP100		0.33
PromoterAI		0.010	Neutral

Splicing

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

Other links and lift over

dbSNP: rs1285968; hg19: chr7-141647022;