NM_001365693.1:c.4770+74T>C

Variant names:

• chr7-142065905-T-C
• rs4276595
• NM_001365693.1:c.4770+74T>C

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00
• Publications: 4 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365693.1. 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
	MGAM	NM_001365693.1	MANE Select	c.4770+74T>C		intron	N/A	NP_001352622.1
	MGAM	NM_004668.3		c.4618+437T>C		intron	N/A	NP_004659.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGAM	ENST00000475668.6	TSL:5 MANE Select	c.4770+74T>C		intron	N/A	ENSP00000417515.2
	MGAM	ENST00000549489.6	TSL:1	c.4618+437T>C		intron	N/A	ENSP00000447378.2
	MGAM	ENST00000620571.1	TSL:5	c.4770+74T>C		intron	N/A	ENSP00000482292.1

Frequencies

GnomAD3 genomes AF: 0.0801 AC: 11567 AN: 144492 Hom.: 1517 Cov.: 28

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

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: 8 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

GnomAD4 genome AF: 0.0803 AC: 11618 AN: 144608 Hom.: 1527 Cov.: 28 AF XY: 0.0777 AC XY: 5473 AN XY: 70418

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: 3 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: 23 AN: 282

European-Non Finnish (NFE) AF: 0.0356 AC: 2277 AN: 63968

Other (OTH) AF: 0.0766 AC: 153 AN: 1998

Alfa AF: 0.0634 Hom.: 201

Asia WGS AF: 0.0320 AC: 110 AN: 3434

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.13
DANN	Benign	0.44
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4276595; hg19: chr7-141765705;