7-141927349-G-A

Position:

• chr7-141927349-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLEC5A	NM_013252.3			downstream_gene_variant		ENST00000546910.6
CLEC5A	NM_001301167.2			downstream_gene_variant
CLEC5A	XM_011515995.3			downstream_gene_variant
CLEC5A	XR_007059995.1			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MGAM	ENST00000465654.5	c.-179-18472G>A		intron_variant		3
MGAM	ENST00000497554.1	n.37-2428G>A		intron_variant, non_coding_transcript_variant		3
CLEC5A	ENST00000546910.6			downstream_gene_variant		1	NM_013252.3	P4

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

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.167

Gnomad4 OTH exome AF: 0.500

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

Gnomad4 AFR AF: 0.612

Gnomad4 AMR AF: 0.465

Gnomad4 ASJ AF: 0.551

Gnomad4 EAS AF: 0.217

Gnomad4 SAS AF: 0.416

Gnomad4 FIN AF: 0.521

Gnomad4 NFE AF: 0.522

Gnomad4 OTH AF: 0.514

Alfa AF: 0.516 Hom.: 22295

Bravo AF: 0.525

Asia WGS AF: 0.315 AC: 1096 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.82
DANN	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1285933; hg19: chr7-141627149;