rs6976028

Variant names:

• chr7-141912917-C-T
• rs6976028
• ENST00000465654.5:c.-180+5049C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000465654.5(MGAM):​c.-180+5049C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 151,968 control chromosomes in the GnomAD database, including 5,788 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 0.26 (5788 hom., cov: 32)
• Consequence: MGAM ENST00000465654.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.327

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MGAM	ENST00000465654.5	c.-180+5049C>T		intron_variant	Intron 1 of 5	3		ENSP00000419372.1
MGAM	ENST00000497554.1	n.36+5049C>T		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39169 AN: 151850 Hom.: 5790 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.442

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.273

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

GnomAD4 genome AF: 0.258 AC: 39176 AN: 151968 Hom.: 5788 Cov.: 32 AF XY: 0.261 AC XY: 19351 AN XY: 74234

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.343

Gnomad4 ASJ AF: 0.319

Gnomad4 EAS AF: 0.442

Gnomad4 SAS AF: 0.305

Gnomad4 FIN AF: 0.280

Gnomad4 NFE AF: 0.306

Gnomad4 OTH AF: 0.277

Alfa AF: 0.301 Hom.: 5223

Bravo AF: 0.257

Asia WGS AF: 0.367 AC: 1276 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.4
DANN	Benign	0.91

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6976028; hg19: chr7-141612717;