dbSNP rs4276595: MGAM:c.4770+74T>C (chr7-142065905-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001365693.1(MGAM):c.4770+74T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0421 in 1,180,072 control chromosomes in the GnomAD database, including 5,618 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 0.080 ( 1527 hom., cov: 28)

Exomes 𝑓: 0.037 ( 4091 hom. )

Consequence

MGAM
NM_001365693.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.00

Publications

4 publications found

Variant links:

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)

MGAM links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MGAM	NM_001365693.1 link	c.4770+74T>C		intron_variant	Intron 40 of 70	ENST00000475668.6	NP_001352622.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
MGAM	ENST00000475668.6 link	c.4770+74T>C	intron_variant	Intron 40 of 70	5	NM_001365693.1	ENSP00000417515.2
MGAM	ENST00000549489.6 link	c.4618+437T>C	intron_variant	Intron 38 of 47	1		ENSP00000447378.2
MGAM	ENST00000620571.1 link	c.4770+74T>C	intron_variant	Intron 40 of 47	5		ENSP00000482292.1

Frequencies

GnomAD3 genomes

AF:

0.0801

AC:

11567

AN:

144492

Hom.:

1517

Cov.:

show subpopulations

Gnomad AFR

AF:

0.196

Gnomad AMI

AF:

0.00708

Gnomad AMR

AF:

0.0423

Gnomad ASJ

AF:

0.0424

Gnomad EAS

AF:

0.000608

Gnomad SAS

AF:

0.0410

Gnomad FIN

AF:

0.0209

Gnomad MID

AF:

0.0822

Gnomad NFE

AF:

0.0356

Gnomad OTH

AF:

0.0774

GnomAD4 exome

AF:

0.0367

AC:

38052

AN:

1035464

Hom.:

4091

AF XY:

0.0365

AC XY:

18955

AN XY:

519014

show subpopulations

African (AFR)

AF:

0.201

AC:

5457

AN:

27084

American (AMR)

AF:

0.0287

AC:

784

AN:

27332

Ashkenazi Jewish (ASJ)

AF:

0.0415

AC:

840

AN:

20226

East Asian (EAS)

AF:

0.000222

AC:

AN:

35956

South Asian (SAS)

AF:

0.0458

AC:

3074

AN:

67058

European-Finnish (FIN)

AF:

0.0172

AC:

783

AN:

45598

Middle Eastern (MID)

AF:

0.0630

AC:

293

AN:

4650

European-Non Finnish (NFE)

AF:

0.0324

AC:

24684

AN:

761898

Other (OTH)

AF:

0.0466

AC:

2129

AN:

45662

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

1352

2704

4057

5409

6761

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

868

1736

2604

3472

4340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0803

AC:

11618

AN:

144608

Hom.:

1527

Cov.:

AF XY:

0.0777

AC XY:

5473

AN XY:

70418

show subpopulations

African (AFR)

AF:

0.197

AC:

8018

AN:

40780

American (AMR)

AF:

0.0422

AC:

608

AN:

14408

Ashkenazi Jewish (ASJ)

AF:

0.0424

AC:

141

AN:

3322

East Asian (EAS)

AF:

0.000610

AC:

AN:

4920

South Asian (SAS)

AF:

0.0419

AC:

189

AN:

4510

European-Finnish (FIN)

AF:

0.0209

AC:

200

AN:

9572

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.0356

AC:

2277

AN:

63968

Other (OTH)

AF:

0.0766

AC:

153

AN:

1998

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

399

797

1196

1594

1993

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

224

336

448

560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0634

Hom.:

201

Asia WGS

AF:

0.0320

AC:

110

AN:

3434

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.13

(source)

DANN

Benign

0.44

PhyloP100

-2.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over