rs6976028

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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]

MGAM Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGAM	ENST00000465654.5	TSL:3	c.-180+5049C>T		intron	N/A	ENSP00000419372.1	E7EW87
	MGAM	ENST00000497554.1	TSL:3	n.36+5049C>T		intron	N/A

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

African (AFR) AF: 0.108 AC: 4495 AN: 41462

American (AMR) AF: 0.343 AC: 5237 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.319 AC: 1107 AN: 3470

East Asian (EAS) AF: 0.442 AC: 2274 AN: 5148

South Asian (SAS) AF: 0.305 AC: 1470 AN: 4818

European-Finnish (FIN) AF: 0.280 AC: 2947 AN: 10512

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.306 AC: 20832 AN: 67972

Other (OTH) AF: 0.277 AC: 585 AN: 2114

Alfa AF: 0.294 Hom.: 7131

Bravo AF: 0.257

Asia WGS AF: 0.367 AC: 1276 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.4
DANN	Benign	0.91
PhyloP100		-0.33

Splicing

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

Other links and lift over

dbSNP: rs6976028; hg19: chr7-141612717;