7-142040277-G-T

Variant names:

• chr7-142040277-G-T
• rs2960753
• NM_001365693.1:c.2373+106G>T

Variant summary

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

The NM_001365693.1(MGAM):​c.2373+106G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 879,158 control chromosomes in the GnomAD database, including 62,119 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 0.33 (9089 hom., cov: 32)
  • Exomes 𝑓: 0.38 (53030 hom.)
• Consequence: MGAM NM_001365693.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.391 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.2373+106G>T		intron	N/A	NP_001352622.1
	MGAM	NM_004668.3		c.2373+106G>T		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.2373+106G>T		intron	N/A	ENSP00000417515.2
	MGAM	ENST00000549489.6	TSL:1	c.2373+106G>T		intron	N/A	ENSP00000447378.2
	MGAM	ENST00000490593.1	TSL:3	n.233G>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50531 AN: 151898 Hom.: 9087 Cov.: 32

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.321

GnomAD4 exome AF: 0.377 AC: 273916 AN: 727142 Hom.: 53030 Cov.: 10 AF XY: 0.377 AC XY: 142074 AN XY: 377240

African (AFR) AF: 0.188 AC: 3344 AN: 17822

American (AMR) AF: 0.381 AC: 10577 AN: 27758

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 6978 AN: 19322

East Asian (EAS) AF: 0.190 AC: 6197 AN: 32682

South Asian (SAS) AF: 0.368 AC: 21780 AN: 59178

European-Finnish (FIN) AF: 0.388 AC: 18407 AN: 47482

Middle Eastern (MID) AF: 0.343 AC: 1467 AN: 4282

European-Non Finnish (NFE) AF: 0.398 AC: 192292 AN: 482916

Other (OTH) AF: 0.361 AC: 12874 AN: 35700

GnomAD4 genome AF: 0.332 AC: 50540 AN: 152016 Hom.: 9089 Cov.: 32 AF XY: 0.335 AC XY: 24863 AN XY: 74310

African (AFR) AF: 0.199 AC: 8267 AN: 41490

American (AMR) AF: 0.390 AC: 5948 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 1227 AN: 3466

East Asian (EAS) AF: 0.207 AC: 1072 AN: 5172

South Asian (SAS) AF: 0.355 AC: 1704 AN: 4804

European-Finnish (FIN) AF: 0.407 AC: 4293 AN: 10546

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.395 AC: 26852 AN: 67960

Other (OTH) AF: 0.318 AC: 670 AN: 2104

Alfa AF: 0.382 Hom.: 5881

Bravo AF: 0.324

Asia WGS AF: 0.242 AC: 840 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.37
DANN	Benign	0.71
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs2960753; hg19: chr7-141740077; COSMIC: COSV72074574;