7-142040277-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001365693.1(MGAM):​c.2373+106G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000686 in 728,860 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000069 (0 hom.)
• Consequence: MGAM NM_001365693.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MGAM	NM_001365693.1	c.2373+106G>C		intron_variant	Intron 20 of 70	ENST00000475668.6	NP_001352622.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MGAM	ENST00000475668.6	c.2373+106G>C		intron_variant	Intron 20 of 70	5	NM_001365693.1	ENSP00000417515.2
MGAM	ENST00000549489.6	c.2373+106G>C		intron_variant	Intron 20 of 47	1		ENSP00000447378.2
MGAM	ENST00000490593.1	n.233G>C		non_coding_transcript_exon_variant	Exon 2 of 2	3
MGAM	ENST00000620571.1	c.2373+106G>C		intron_variant	Intron 20 of 47	5		ENSP00000482292.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000686 AC: 5 AN: 728860 Hom.: 0 Cov.: 10 AF XY: 0.00000793 AC XY: 3 AN XY: 378122

African (AFR) AF: 0.00 AC: 0 AN: 17838

American (AMR) AF: 0.00 AC: 0 AN: 27810

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19362

East Asian (EAS) AF: 0.00 AC: 0 AN: 32698

South Asian (SAS) AF: 0.00 AC: 0 AN: 59328

European-Finnish (FIN) AF: 0.0000210 AC: 1 AN: 47544

Middle Eastern (MID) AF: 0.000233 AC: 1 AN: 4290

European-Non Finnish (NFE) AF: 0.00000620 AC: 3 AN: 484232

Other (OTH) AF: 0.00 AC: 0 AN: 35758

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.38
DANN	Benign	0.49
PhyloP100		-1.5

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;