rs4726481

Variant names:

• chr7-141968603-G-T
• rs4726481
• ENST00000465654.5:c.-3+22606G>T

Variant summary

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

The ENST00000465654.5(MGAM):​c.-3+22606G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 151,460 control chromosomes in the GnomAD database, including 13,894 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 0.43 (13894 hom., cov: 32)
• Consequence: MGAM ENST00000465654.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.54
• Publications: 8 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=-1.06).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.533 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.-3+22606G>T		intron_variant	Intron 2 of 5	3		ENSP00000419372.1

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64513 AN: 151342 Hom.: 13871 Cov.: 32

Gnomad AFR AF: 0.448

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.542

Gnomad ASJ AF: 0.458

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.460

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

GnomAD4 genome AF: 0.426 AC: 64577 AN: 151460 Hom.: 13894 Cov.: 32 AF XY: 0.427 AC XY: 31583 AN XY: 73960

African (AFR) AF: 0.449 AC: 18543 AN: 41332

American (AMR) AF: 0.543 AC: 8278 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.458 AC: 1585 AN: 3462

East Asian (EAS) AF: 0.498 AC: 2568 AN: 5158

South Asian (SAS) AF: 0.331 AC: 1590 AN: 4804

European-Finnish (FIN) AF: 0.346 AC: 3616 AN: 10442

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.400 AC: 27088 AN: 67714

Other (OTH) AF: 0.462 AC: 970 AN: 2098

Alfa AF: 0.416 Hom.: 3829

Bravo AF: 0.443

Asia WGS AF: 0.417 AC: 1429 AN: 3430

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.12
DANN	Benign	0.16
PhyloP100		-3.5

Splicing

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

Other links and lift over

dbSNP: rs4726481; hg19: chr7-141668403;