chr7-141993008-T-G

Variant names:

• chr7-141993008-T-G
• rs6947481
• ENST00000465654.5:c.-2-12521T>G

Variant summary

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

The ENST00000465654.5(MGAM):​c.-2-12521T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 152,144 control chromosomes in the GnomAD database, including 4,664 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 0.22 (4664 hom., cov: 32)
• Consequence: MGAM ENST00000465654.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.597
• Publications: 2 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.382 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGAM	ENST00000465654.5	TSL:3	c.-2-12521T>G		intron	N/A	ENSP00000419372.1

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33142 AN: 152030 Hom.: 4643 Cov.: 32

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.218 AC: 33216 AN: 152144 Hom.: 4664 Cov.: 32 AF XY: 0.221 AC XY: 16403 AN XY: 74382

African (AFR) AF: 0.387 AC: 16049 AN: 41460

American (AMR) AF: 0.194 AC: 2960 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 530 AN: 3470

East Asian (EAS) AF: 0.325 AC: 1680 AN: 5174

South Asian (SAS) AF: 0.227 AC: 1094 AN: 4824

European-Finnish (FIN) AF: 0.135 AC: 1428 AN: 10600

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8938 AN: 68008

Other (OTH) AF: 0.204 AC: 430 AN: 2110

Alfa AF: 0.165 Hom.: 8423

Bravo AF: 0.230

Asia WGS AF: 0.293 AC: 1017 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.43
PhyloP100		-0.60

Splicing

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

Other links and lift over

dbSNP: rs6947481; hg19: chr7-141692808;